peplomycin and Carcinoma--Squamous-Cell

Topics: Aged; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Humans; Lip Neoplasms; Male; Peplomycin; Scleroderma, Diffuse

The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Lymphatic Metastasis; Middle Aged; Mitomycin; Neoadjuvant Therapy; Organoplatinum Compounds; Peplomycin; Prognosis; Survival Rate; Uterine Cervical Neoplasms

Both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are very common in skin malignancy. Operative therapy is the first choice at the treatment for SCC and BCC in early stage. After excision for large skin tumor, occasionally we use skin flap or musculocutaneous flap or free flap. At the old patient of Stage III and IV SCC and BCC, sometimes reduction surgery is useful at the combination therapy. Radiation as adjuvant therapy is sometimes useful for not only SCC but also BCC. The clinical efficacy of CA (C' A') chemotherapy (CDDP, ADM or CBDCA, EPI-ADM), was evaluated on Stage III, IV SCC and BCC. The response rate was 63% in SCC and 75% in BCC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Palliative Care; Peplomycin; Prognosis; Radiotherapy, Adjuvant; Skin Neoplasms; Skin Transplantation; Surgical Flaps

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Maxillary Sinus Neoplasms; Peplomycin; Survival Rate; Tegafur; Uracil

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Male; Methotrexate; Middle Aged; Peplomycin; Remission Induction

Preoperative chemotherapy should be effective against cancers and have few side effects that would prevent surgery. We investigated the histological effects and side effects of low- and high-dose CDDP chemotherapy against oral squamous cell carcinoma (SCC), and discuss the therapeutic benefits of each regimen. Thirty-six patients were divided into two groups as follows, in a non-randomized manner: A) low-dose CDDP (17 patients): CDDP 5 mg/m2/day + UFT 400 mg/day (day 1-5) (1 or 2 courses), B) high-dose CDDP (19 patients): CDDP 70-100 mg/m2/day (day 1) + peplomycin 5 mg/day (day 2-6) (1 or 2 courses). Curative surgery was conducted 1 week after protocol A or 2-3 weeks after protocol B. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical materials of primary tumors. In this classification, grade IIB, III and IV were as effective. Maximum histological effect was seen with grade IIB for regimen A and grade IV for regimen B. Four of 17 patients (23.5%) responded to regimen A and 13 of 19 patients (68.4%) to regimen B. Side effects, such as nausea, vomiting and myelosuppression, appeared with regimen B, but were seen little with regimen A. The 2-year survival rate was 93.3% with regimen A and 78.9% with regimen B. With regimen A, the 2-year survival rate of effective cases was 100% and that of ineffective cases was 91.7%. With regimen B, the rate was 92.3% and 50.0%, respectively. Effective cases showed good prognosis in both groups. The low-dose CDDP regimen was not so effective against primary tumors histologically, but the prognosis was good. The low-dose CDDP regimen appears to be useful for preoperative chemotherapy of oral SCC.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Peplomycin; Survival Rate; Treatment Outcome

To evaluate the response rate and toxicity and to improve survival, neoadjuvant chemotherapy (NAC) was utilized in patients younger than 50 years with locally advanced cervical squamous cell carcinoma.. Twenty-one patients were treated with preoperative NAC. Eligibility included patients with previously untreated stage IB or IIA with deep stromal invasion assessed by magnetic resonance imaging or bulky tumor or IIB squamous cell carcinoma who were younger than 50 years. The NAC consisted of cisplatin (60 mg/m(2)) on day 1, vinblastine (4 mg/m(2)/day) on days 1 and 2, and peplomycin (10 mg/day) on days 1, 8, and 15 (PVP). Treatment was repeated every 3 weeks for a total of two cycles. All 21 patients underwent radical hysterectomy following NAC. Postoperative radiotherapy was given to 18 patients. We used 21 patients who underwent radical hysterectomy and postoperative radiation therapy as a nonrandomized control group.. The response rate for NAC was 86% (18/21). Two patients required discontinuation of PVP treatment after one administration because of grade 4 neutropenia and thrombocytopenia, and decreased carbon monoxide diffusion capacity, respectively. In the NAC group, stromal invasion was significantly reduced (P = 0.0103), and the incidence of lymph node metastasis was decreased. No patients had positive parametrial and vaginal margins. The overall 5-year survival rate was 84.0% in the NAC group, which was significantly better than that in the control group (58.9%) (P = 0.0434).. NAC for younger patients with locally advanced cervical carcinoma is thought to be safe, well tolerated, effective, and useful for increasing operability, decreasing pathological risk factors, and improving survival.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Peplomycin; Risk Factors; Uterine Cervical Neoplasms; Vinblastine

To formulate and evaluate a facial arterial infusion chemotherapy for squamous cell lip carcinoma.. The study included six patients (age range, 46-84 years) with squamous cell carcinoma of the lower lip. There were two T1 tumors, three T2 tumors, and one T1-compatible postoperative recurrent tumor. A 4-F, double-lumen balloon catheter was inserted into the external carotid artery through the superficial temporal artery and placed for selective infusion into the tumor-feeding facial artery. Patients received a combination of mitomycin C (4.4 mg/m2 per body surface area) on day 1 and 3.2 mg/m2 of peplomycin sulfate on days 1-7 (22.4 mg/m2 per week), or, when peplomycin sulfate was contraindicated, 16 mg/m2 of cisplatin only on days 1-5 (80 mg/m2 per week). Two to three cycles of chemotherapy were given until tumor disappearance was histologically confirmed.. Complete tumor disappearance was achieved in all cases. One patient had a self-limiting asthma attack during peplomycin sulfate treatment, and another had transient partial hair loss. No disfigurement, recurrence, or late complications were observed at a mean follow-up of 5.0 years (range, 2.3-11.2 years).. The described facial arterial infusion chemotherapy appears to be a safe and curative treatment for T1 and T2 squamous cell lip carcinomas.

Topics: Aged; Aged, 80 and over; Angiography, Digital Subtraction; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Infusions, Intra-Arterial; Lip Neoplasms; Male; Maxillary Artery; Middle Aged; Mitomycin; Peplomycin; Radiography, Interventional

This study was conducted to determine long term survival rates and the pattern of failure in patients with carcinoma of the oral cavity treated with induction chemotherapy or preoperative radiotherapy followed by surgery.. A retrospective analysis was performed of 141 eligible patients with Stage II-IV International Union Against Cancer (UICC) staging system squamous cell carcinoma of the oral cavity at the study department between 1985 and 1994. These patients received one of three treatments: surgery with or without peplomycin chemotherapy (Group A; n = 49); preoperative radiotherapy with or without concomitant peplomycin chemotherapy followed by surgery (Group B; n = 59); and induction chemotherapy followed by surgery (Group C; n = 33). Induction chemotherapy was comprised of two cycles of cisplatin, vincristine, peplomycin, with or without mitomycin C.. When all 141 patients were analyzed, there was no significant difference in overall survival or disease free survival. However, a statistically significant increase in the incidence of neck recurrence in Group C was observed compared with Group A (P = 0.002). Within 79 patients with N0 disease, a statistically significant disadvantage was detected for Group C in terms of disease free survival compared with Group A (P = 0.038). In patients with Stage II disease (50 patients), there was a significant difference in disease free survival, with Group C inferior to both Group A (P = 0.04) and Group B (P = 0.066).. Induction chemotherapy was associated with a significant increase in regional failure for patients with carcinoma of the oral cavity with N0 disease and those with Stage II disease.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mitomycin; Mouth Neoplasms; Neoplasm Recurrence, Local; Peplomycin; Retrospective Studies; Survival Analysis; Vincristine

Between 1985 and 1990, 20 patients with stage 2 and 3 esophageal cancer without esophagopulmonary fistulas were treated with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin). Patients given the combined therapy received courses of chemotherapy during weeks 1 and 6 and radiotherapy during weeks 2-5 and 7-9. Chemotherapy consisted of i.v. cisplatin (80 mg/ m2 of body surface area) on day 1, i.v. methotrexate (40 mg/ m2) on day 2, and s.c. peplomycin (10 mg/day) continuously from day 2 to day 5. Radiotherapy was external irradiation with or without intracavitary irradiation. In seven cases, external irradiation alone was administered at 65-70 Gy, and in 13 cases, external irradiation (50-55 Gy) was combined with intracavitary irradiation (14-20 Gy). At the end of treatment, the rate of complete response was 60% with an overall response rate of 95%. Five-year total survival was 25%; cause-specific survival was 36.8%. The most common acute toxicities were bone marrow suppression, hepatic and renal damage, pneumonitis, and esophagitis. There was no life-threatening toxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Female; Humans; Male; Methotrexate; Middle Aged; Peplomycin; Prospective Studies; Radiotherapy Dosage

Recent advances in chemotherapy have markedly improved the treatment results for oral cancer. Among many chemotherapeutic regimens, the usefulness of multiple combination chemotherapy with cisplatin as the primary drug has been frequently reported. During the past 6-year period, we have performed combination chemotherapy with cisplatin as the primary drug, peplomycin, and etoposide (CPE chemotherapy) as one of the chemotherapeutic regimens for oral cancer. The subjects were 11 patients (7 males and 4 females) with tongue cancer treated by CPE chemotherapy as neoadjuvant chemotherapy at our department between March, 1990 and April, 1995.. PR in 8 (73%), and NC in 3 (27%). No patient showed CR and PD. The side effects observed were reversible findings such as transient myelosuppression, nausea-vomiting, and alopecia. No patient showed severe or persistent suppression of hematopoietic function.

Topics: Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Etoposide; Female; Humans; Male; Middle Aged; Nausea; Peplomycin; Tongue Neoplasms; Vomiting

In the present study, we investigated the clinical and histopathological effects of CP therapy consisting of cisplatin (CDDP 50 mg/m2) or carboplatin (CBDCA 300 mg/m2) and peplomycin (PEP 5 mg/day) for 25 patients with oral squamous cell carcinoma. The effects of treatment and associated complications were as follows: 1) Complete response (CR) was achieved in 8 and partial response (PR) in 14 of the 25 cases. The overall clinical response rate was 88%. The histological response rate was 64%. 2) The clinical effects were not always consistent with the histopathological effects. There were discrepancies between the clinical and histopathological effects, especially in PR determined by clinical findings. 3) The principal adverse reaction was gastro-intestinal disturbances, but symptoms were able to be controlled. Signs of hematologic toxicity and renal disturbance were mild and did not preclude the continuance of therapy. The results of this study indicated that neo-adjuvant chemotherapy with CDDP and PEP was highly effective for the local control of oral squamous cell carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Diarrhea; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Nausea; Peplomycin; Preoperative Care; Prognosis; Tegafur; Uracil; Vomiting

A new dosage formulation consisting of anticancer drugs bound to carbon particles was developed for treating cancers of the upper digestive tract, and is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site, as compared to a drug in aqueous solution form. Thirteen patients with histologically proven carcinoma (8 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), in whom surgical treatment was contraindicated, received intra- and peritumoral injection of the new dosage formulation (total dose of 35-100 mg of peplomycin or 250-500 mg of methotrexate) guided by esophago- or gastro-fiberscope. Eleven of these 13 patients are currently alive, 12-64 months after therapy, or they died without evidence of recurrence 12-98 months after the treatment. One patient has remained cancer-free for 37 months after a second course of the therapy given to treat a recurrence found 26 months after the first treatment. Another patient has a recurrent tumor 9 months after the therapy and is now going to undergo a second course of treatment. Side effects were not severe and well-tolerable.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carbon; Carcinoma, Squamous Cell; Endoscopy, Digestive System; Esophageal Neoplasms; Humans; Injections, Intralesional; Lymphatic Metastasis; Methotrexate; Peplomycin; Prognosis; Stomach Neoplasms; Treatment Outcome

The Japanese Society of Thyroid Surgery undertook a pilot study of treatment for anaplastic thyroid carcinoma in a cooperative setting. The treatment consisted of cisplatin 40 mg/m2 drip intravenous infusion (div), day 1, adriamycin 60 mg/m2 iv, day 1, etoposide 100 mg/m2/day div, days 1-3, peplomycin 5 mg/body/day sc, days 1-5 and granulocyte colony-stimulating factor (G-CSF) 2 micrograms/kg/day sc, days 6-14. This was scheduled to be repeated every 3 weeks. Local radiation therapy was added for patients in whom it was indicated. A total of 17 patients (mean age, 66 yr) were enrolled. Ten patients had advanced disease with measurable lesions and 2 patients experienced partial remission lasting 2 and 3 months, respectively. Six of 7 patients were treated with the same modality of treatment as an adjuvant. Three died of progressive disease after 3-7 months and three others have survived for 3-11 months. The toxicities of the chemotherapy were mainly bone marrow suppression, despite G-CSF support. Transient liver dysfunction was also noticed. These results indicate that this combined a treatment can be given to patients with acceptable toxicity. The degree of leukopenia was greater than expected, partly due to the advanced age of the patients and the low dose of G-CSF. In addition, 8 available thyroid specimens were examined for the mdr 1 gene and P-glycoprotein, but all were negative. Further study of anaplastic thyroid carcinoma by this cooperative group will be carried out.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Male; Middle Aged; Peplomycin; Pilot Projects; Survival Rate; Thyroid Neoplasms; Thyroidectomy

Twenty one patients with resectable oral cancer received two courses of induction chemotherapy with peplomycin (PEP), vincristine (VCR), mitomycin C (MMC) and cisplatin (CDDP). Five patients had a complete response to the therapy and 9 had a partial response. Histological evaluation by Ohboshi-Shimozato classification indicated that Grade IV was obtained in 7 cases, Grade III was in 4 cases. Moreover, the study suggested that this regimen was less effective for metastatic lymph lesions than that for the primary tumors.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Mouth Neoplasms; Peplomycin; Vincristine

In Japan, the role of radiotherapy for gingival carcinomas has not been considered as a radical treatment, but only a pre and/or postoperative treatment. This study was aimed to discuss a possibility of radiotherapy for a radical treatment. In this study, radiotherapy was given as an initial treatment for squamous cell carcinomas of the lower gingiva in simultaneous combination with chemotherapy of bleomycin or peplomycin (Tokyo, Japan).. When complete regression of the tumor was obtained, subsequent surgery was postponed with or without a booster of radiotherapy of about 30 Gy until a recurrent lesion was confirmed.. Sixty-seven percent of 100 patients with T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or T4 had complete regression. The 5-year local control rate by T classification, including the results of secondary treatments (surgery and/or radiotherapy and/or chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and 61% for T4. The 5-year local control rate according to treatment methods was 95% in the group without surgery and 86% in the group with surgery for T1 and T2 patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage II, 71% for Stage III, 51% for Stage IV and 70% overall.. The combination of radiotherapy and chemotherapy could be a conservative radical treatment for T1 and T2 patients with lower gingival carcinoma.

Topics: Bleomycin; Carcinoma, Squamous Cell; Cobalt Radioisotopes; Combined Modality Therapy; Follow-Up Studies; Gingival Neoplasms; Humans; Lip; Mouth Mucosa; Neoplasm Staging; Peplomycin; Radiotherapy

Neoadjuvant chemotherapy consisting of a cis-platinum, vincristine and peplomycin (CVP) combination has been used to treat patients with carcinoma of the uterine cervix at our departments since 1983. Twenty-one patients are reviewed in this study. A high response rate (71.4%) was obtained with 19.0% complete and 52.4% partial responses prior to radical therapy. Survival times and the progression free interval for stage I and III disease treated with CVP show improvement compared to patients not treated with CVP. No life-threatening toxicity related to chemotherapy was noted. This combination chemotherapy used in neoadjuvant setting warrants further study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Peplomycin; Platinum; Survival Rate; Uterine Cervical Neoplasms; Vincristine

Eighty-six patients with non-small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups. In the adjuvant chemotherapy group, patients received cisplatin-based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2.3 (from 1 to 6 cycles). In this trial, no evidence of improved survival or delayed recurrence was seen in the treated patients. In multivariate analysis of prognostic variables, the most important factor was the pathological stage of the disease and, second, DNA ploidy of the primary tumor. Although histology (squamous vs. non-squamous cell carcinoma) had a trend to influence the survival, it was not a significant factor. A total of 33 patients had recurrences: 17 and 16 patients were in control and adjuvant chemotherapy groups, respectively. Postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group, as determined by the generalized Wilcoxon and log rank tests. Median survival time after recurrence in the control and adjuvant therapy groups was 18.5 and 7.5 months, respectively. These results suggest that DNA ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy. Furthermore, analysis of postrecurrent survival in the adjuvant chemotherapy trial, as well as that of overall and disease-free survivals should be done.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cyclophosphamide; DNA, Neoplasm; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Neoplasm Staging; Peplomycin; Ploidies; Prognosis; Vindesine

Oral squamous cell carcinoma is the commonest male (29%) and the second commonest female (18%) malignancy in South India. At first attendance 93% of the tumours are stage T3 or T4. They are essentially locoregional, remote metastases being rare (0.75%). Radiotherapy alone yields a poor survival (19% 5 year NED). Radiopotentiation by chemical sensitizers and cytotoxic drugs has been attempted since 1960, the best results being obtained by a combination of irradiation and bleomycin. There was, however, persistent failure in about 40% of cases. The present three-armed trial attempted to improve the results of radiotherapy and bleomycin by the addition of hyperthermia. A total of 101 T3 and T4 buccal squamous cancers were entered in the trial over a period of nearly three years. Entry closed in August 1987 and the last case was evaluated in October 1987, hence only response data are available. Hyperthermia did not confer any benefit.

Topics: Adult; Aged; Bleomycin; Carcinoma, Squamous Cell; Cheek; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Peplomycin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials as Topic; Double-Blind Method; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vincristine

From March 1983 to February 1985, we treated 74 patients (pts) with inoperable non-small cell lung cancer. Twenty-seven pts with squamous cell carcinoma were randomized between regimen PMP (CDDP 60 mg/m2, d 1, MMC 6 mg/m2, d 3, d 10 and PEP 5 mg/m2, d 3-7) and regimen PM (CDDP 60 mg/m2, d 1 and MMC 6 mg/m2, d 3, d 10). Forty-seven pts with adenocarcinoma and large cell carcinoma were randomized between regimen PMF (CDDP 60 mg/m2, d 1, MMC 6 mg/m2, d 3, d 10 and FT 800 mg/body, d 3-21) and regimen PM. The response rates of evaluable cases (EC) were as follows: Squamous cell carcinoma; Regimen PMP 50% (1 CR + 4 PR/10 EC). Regimen PM 40% (4 PR/10 EC). Adenocarcinoma plus large cell carcinoma; Regimen PMF 13.6% (3 PR/22 EC). Regimen PM 11.1% (2 PR/18 EC). The median survival time (MST) was increased from 23 weeks in non-responders to 32 weeks in responders. However, the difference between the survival curves for responders and non-responders was not statistically significant. Of the toxic effects shown in all 74 registered pts, hematological (64.9%), gastrointestinal (60.8%) and renal (31.1%) toxicities were the common complications. We concluded that regimen PMP was more useful than regimen PM for pts with squamous cell carcinoma but that regimen PMF demonstrated no appreciable difference, compared with regimen PM for pts with adenocarcinoma and large cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Random Allocation; Tegafur

The effects of two chemotherapeutic regimens, peplomycin (PLM) plus carbazilquinone and PLM plus mitomycin, on non-small cell carcinoma of the lung were evaluated by a randomized controlled trial. Seven partial responses were observed in 53 evaluable patients, for an overall response rate of 13.2%. There was no difference in response rate or in median survival time between PLM plus carbazilquinone (11.5% and 32 weeks) and PLM plus mitomycin (14.8% and 25 weeks). Seven patients developed interstitial pneumonitis, and four died of pulmonary fibrosis. It was concluded that the chemotherapeutic regimens that include PLM are only marginally effective against non-small cell carcinoma of the lung, with relatively frequent pulmonary fibrosis.

Topics: Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Azirines; Bleomycin; Carbazilquinone; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycins; Peplomycin; Random Allocation

A new bleomycin derivative NK631 was administered in five cases of advanced recurrent oral carcinoma. The visible improvement of the tumor was noted in three cases, and in the cases of lower lip carcinoma the tumor completely disappeared, however, there was no effective change in cases of cervical metastases of the floor of the mouth and tongue carcinoma. The peripheral lymphocyte counts and serum proteins disclosed a characteristic decrease, serum proteins decreased in the albumin fraction and slightly increased in alpha 2-globlin fraction. Main side effects of NK 631 were skin exanthema, alopecia, anorexia, pyrexia, fatigue and bleeding from the tumor lesion. Regarding the lung function, the vital capacity did not change, but PaO and PaCO in blood gas analysis were together observed to slightly decrease, and it may be supposed that the influence of NK631 on the lung function cannot be neglected. T-cell ratio, lymphocyte blastoformation following PHA stimulation, PPD and DNCB skin tests, and phagocytosis test of peripheral leucocytes were studied. The immuno-suppressive effect of KK631 was the same or weak as bleomycin.

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Clinical Trials as Topic; Female; Humans; Immunologic Techniques; Lip Neoplasms; Lymphocytes; Male; Middle Aged; Mouth Neoplasms; Peplomycin; Tongue Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lip; Peplomycin

The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Fluorouracil; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Peplomycin; Taxoids

The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence.. We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato.. Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively.. The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Follow-Up Studies; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Lymphatic Irradiation; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoadjuvant Therapy; Peplomycin; Pneumonia, Aspiration; Radiotherapy Dosage; Radiotherapy, Conformal; Retrospective Studies; Treatment Outcome; Xerostomia

Continuous intra-arterial (IA) administration of peplomycin (PEP) through a tumor-feeding artery is one of the most effective treatments for cutaneous squamous cell carcinoma (cSCC) in cosmetic areas.. In order to determine the effective and safe dose of PEP and the curative rate of IA-PEP, we retrospectively investigated a case series of 24 patients with cSCC on the lips who were treated with IA-PEP.. IA-PEP reduced the tumor mass in all 24 cases (100%). A complete response occurred in 17 patients (70.8%), and a partial response occurred in seven (29.2%). Moreover, 17 patients (70.8%) were cured, three patients developed cervical lymph node metastasis (12.5%), and four developed local recurrence (16.7%). Three out of the 24 patients developed interstitial pneumonia (12.5%).. Low-dose IA-PEP administered through a superficial temporal artery was a highly effective treatment that achieved a curative response for 70.8% of patients with cSCC on the lips.

Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Female; Humans; Infusions, Intra-Arterial; Lip Neoplasms; Male; Middle Aged; Neoplasm Staging; Peplomycin; Prognosis; Retrospective Studies; Skin Neoplasms; Temporal Arteries

Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for cutaneous squamous cell carcinoma (SCC) on cosmetic areas. Although this reagent is useful for the treatment of SCC, its immunomodulatory effect on the tumor microenvironment is still unknown.. In this study, we investigated the immunomodulatory effects of PEP on the tumor-infiltrating regulatory T cells and tumor-associated macrophages as well as CD8(+)TIA-1(+) cytotoxic T cells in the lesional skin of 5 patients with SCC on the lips.. Our data suggest that, in addition to the direct antitumor effects, PEP decreased immunosuppressive cells and increased cytotoxic T lymphocytes at the tumor sites, which might maintain antitumor immune response against SCC.

Topics: Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Humans; Immunomodulation; Infusions, Intra-Arterial; Lip; Macrophages; Neovascularization, Pathologic; Peplomycin; Skin Neoplasms; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory

Levels of 5-FU metabolic or related enzymes, particularly thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), have been investigated in various cancer types, including uterine cervical cancer. Intratumoral TP levels have been reported to increase in response to several chemotherapeutic agents or irradiation in both xenografts and clinical studies. In cervical cancer, however, only a few studies about changes in TP and DPD expression associated with cancer treatment have been published. We evaluated the effect of chemotherapy and/or irradiation on TP and DPD expression in cervical squamous cell carcinoma.. Of 27 patients in this study, 12 patients underwent neoadjuvant chemotherapy consisting of nedaplatin, ifosfamide, and/or peplomycin followed by radical surgery, and 15 patients underwent radiotherapy (n=8) or chemoradiotherapy with nedaplatin (n=7) as initial treatment. Tumor specimens were obtained from biopsies acquired before treatment and after administration of chemotherapy (2 weeks after the first and second cycles), and after irradiation with 10 Gy, 20 Gy, and 30 Gy. These specimens were used to measure TP and DPD levels by ELISA.. In the 12 patients who received neoadjuvant chemotherapy, intratumoral TP and DPD levels did not change. In contrast, in the 15 patients who underwent radiotherapy or chemoradiotherapy with nedaplatin, TP or DPD expression appeared to be slightly increased or decreased, respectively, after irradiation with 20 Gy, and consequently the TP/DPD ratio was significantly higher after irradiation with 20 Gy than before irradiation.. These results suggest a clinical advantage of chemoradiotherapy with capecitabine or doxyfluridine over radiotherapy alone via the elevation of the TP/DPD ratio in cervical squamous cell carcinoma. However, no advantage of combination chemotherapy with these 5-FU derivatives was demonstrated. Therefore, further evaluation with a larger number of patients or with other chemotherapeutic agents is required to confirm these observations.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Carcinoma, Squamous Cell; Chemoradiotherapy; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Female; Floxuridine; Fluorouracil; Humans; Ifosfamide; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Peplomycin; Thymidine Phosphorylase; Uterine Cervical Neoplasms

The presence or absence of metastasis bears an important influence on the prognosis of head and neck cancer patients. Neoadjuvant chemotherapy has become widely employed as an initial treatment. However, the actual effectiveness of neoadjuvant chemotherapy on metastasis is still unestablished. Therefore, using an orthotopic implantation model in which cervical lymph node metastasis of oral squamous cell carcinoma can be reproduced, we investigated the inhibitory effect of neoadjuvant chemotherapy on metastasis. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19 cells, was implanted into the tongues of nude mice. After implantation, the mice were divided into four groups: S (surgery), C+S (preoperative chemotherapy+surgery), S+C (surgery+postoperative chemotherapy), and a control (nontreatment) groups. The treatment (tumor resection or chemotherapy) was started 7 days postimplantation. The effects of each treatment on cervical lymph node metastasis were investigated by examining the rate of lymph node metastasis formation at 28 days postimplantation. In the control group, five of the 11 mice died of cachexia before the end of the experiment. However, all mice in the S, C+S, and S+C groups survived until 28 days after implantation. The cervical lymph node metastasis rates were 81.8% in S, 18.1% in C+S, 63.6% in S+C, and 100% in control groups. Thus, metastasis to the cervical lymph node was markedly inhibited by the combination of neoadjuvant chemotherapy and tumor resection. The findings of this study indicate that neoadjuvant chemotherapy is effective for inhibiting metastasis, and that it is necessary to begin chemotherapy as early as possible to achieve an inhibitory effect on metastasis. Considering these effects, if anticancer drugs are used, better therapeutic results can be expected.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Disease Models, Animal; Female; Humans; Lymphatic Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neck; Neoadjuvant Therapy; Peplomycin; Tongue Neoplasms; Treatment Outcome

The purpose of this study was to clarify outcome for concurrent chemoradiation (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized retrospective analysis of 226 patients treated with definitive CT-RT or radiotherapy alone (RT alone) in nine institutions between 2001 and 2003. External irradiation consisted of whole pelvic irradiation and pelvic side wall boost irradiation, using a central shield during the latter half of the treatment with the anteroposterior parallel opposing technique. The external beam irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy, platinum based drugs were used alone or in combination with other drugs such as 5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone, respectively. There was no significant difference between CT-RT and RT for overall survival and disease free survival. Univariate analysis suggested that loco-regional control was better with CT-RT, but multivariate analysis could not confirm this finding. Compared to RT alone, CT-RT caused significantly more acute and late complications. Thus, late complication (grade 3-4) free survival rate at 50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window with concomitant radiochemotherapy and HDR brachytherapy may be narrow, necessitating a close control of dose volume parameters and adherence to systems for dose prescription.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Lymphatic Irradiation; Middle Aged; Mitomycin; Organoplatinum Compounds; Peplomycin; Radiotherapy Dosage; Retrospective Studies; Survival Analysis; Uterine Cervical Neoplasms; Vincristine

Intra-arterial neoadjuvant chemotherapy (TPP) with pirarubicin, cisplatin and peplomycin produced strong primary effects on oral squamous cell carcinoma, using metoclopramide (MCA) as an anti-emetic. After clinical application of granisetron (GRN), the clinical responses to TPP observed previously were weakened. In this paper, the influence of GRN on TPP is discussed. Sixty-three cases were evaluated with regard to the primary effects of TPP and anti-emetics. GRN was used in 42 cases of the GRN group, and MCA in 21 cases of non-GRN group. The clinical response rate (complete response, CR or partial response, PR) was 95.2% in the non-GRN group, and 76.2% in the GRN group. The rate of CR in the non-GRN group was 47.6%, whereas it was 9.5% in the GRN group. The histological effects in the GRN group were significantly lower (P<0.05) than those of non-GRN group. Concerning the relationship between the clinical responses and the histological responses, 4 of the 18 CR+PR cases (22.2%) in the GRN group showed good histological responses, compared with 6 of the 14 CR+PR cases (42.9%) showing in the non-GRN group. The histological responses in the GRN group were significantly lower (P<0.05) than in the non-GRN group. Our data indicate that GRN reduces the clinical and histological responses of chemotherapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chi-Square Distribution; Cisplatin; Cohort Studies; Doxorubicin; Drug Interactions; Female; Granisetron; Humans; Injections, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Peplomycin; Retrospective Studies

The aim of this study is to establish Japanese national practice patterns for uterine cervical cancer patients who received radiotherapy without surgery.. The Japanese Patterns of Care Study (JPCS) conducted a national survey of 73 institutions using two-stage cluster sampling, and collected specific information on 591 patients with uterine cervical cancer treated by radiotherapy without planned surgery between 1995 and 1997.. The median age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90 for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam energy utilized varied significantly by institution strata. Midline block was used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was performed in 77%. Institution strata correlated significantly with the ICBT application. The majority of patients (89%) were treated with high-dose-rate (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The median overall treatment time including ICBT was 49 days. Twenty-four percent of the patients received chemotherapy. Concurrent chemoradiation was performed in 5%.. The JPCS established the Japanese national practice patterns of care for uterine cervical cancer patients treated with radiotherapy without planned surgery between 1995 and 1997. This survey demonstrated that the institutional strata significantly affected several practice patterns.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brachytherapy; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Female; Fluorouracil; Health Care Surveys; Humans; Middle Aged; Neoplasm Staging; Peplomycin; Practice Patterns, Physicians'; Radiotherapy Dosage; Uterine Cervical Neoplasms

Cisplatin (CDDP) is widely used for chemotherapy of oral squamous cell carcinoma (OSCC). However, the mechanism of resistance to CDDP is unclear. Recently, caveolin-1 was identified as being associated with both metastasis and multidrug resistance. In the present study, we showed that caveolin-1 expression is significantly related to chemosensitivity in OSCC.. We established a CDDP-resistant cell line, H-1R, from the parental OSCC cell line, H-1. Caveolin-1 expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in both cell lines. We analyzed expression of caveolin-1 in 30 OSCC biopsy specimens and investigated the relationship between expression of caveolin-1 and patients' clinicopathological parameters and chemotherapeutic responses.. The 3-(3,4-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that H-1R has a ten-times greater resistance to CDDP than H-1 has. The level of caveolin-1 expression in H-1R was significantly decreased in comparison with that in H-1 by real-time RT-PCR analysis. Positive caveolin-1 immunostaining correlated positively with a complete response (16/20, 80.0%). However, negative immunostaining was found in 6/7 (85.7%) cases with no response. Positive immunohistochemical staining of caveolin-1 correlated positively with chemosensitivity to CDDP-based combination chemotherapy (P=0.02).. These results suggest that overexpression of the caveolin-1 gene may provide novel diagnostic markers associated with CDDP sensitivity in OSCC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Caveolin 1; Caveolins; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Female; Gene Expression; Gingival Neoplasms; Humans; Male; Middle Aged; Peplomycin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Transfection; Treatment Outcome; Tumor Cells, Cultured; Vinblastine

This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy.. A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients.. The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P < 0.0001) and T classification (P < 0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P < 0.0005) and T classification (P < 0.05) were identified as significant prognostic factors for LCP and OAS.. This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Male; Maxillary Sinus Neoplasms; Middle Aged; Neoadjuvant Therapy; Peplomycin; Prognosis; Radiotherapy Dosage; Retrospective Studies; Treatment Outcome

A rare case of Stevens-Johnson syndrome (SJS) due to peplomycin in a 48-year-old man is described. The patient had squamous cell carcinoma on the scalp and underwent preoperative neoadjuvant chemotherapy with peplomycin. On the fifth day of the chemotherapy, he developed a fever and multiple dusky violaceous erythematous areas and pustules on his trunk, thighs, and palms. Erosive erythema and erosions also developed on his soles, scrotum, and oral mucosa. A biopsy specimen taken from the eruption on the thigh revealed marked liquefaction degeneration of the basal layer of the epidermis. Laboratory examinations demonstrated aggravation of liver function. Additionally, the patient developed conjunctivitis and corneal erosions. Although he had some subcorneal pustules, we diagnosed the case as an unusual form of SJS because of severe mucous membrane involvement. Oral prednisolone was administered, and the symptoms subsided. Then the patient underwent wide local excision. One month after surgery, we performed patch tests and a lymphocyte stimulation test with negative results. Then we re-administered peplomycin starting with 1/20 of a daily dose and gradually increasing the dose each day. After administration of the regular daily dose, the patient had a relapse of fever, eruptions, stomatitis, corneal erosions, and liver dysfunction. Therefore, a definite diagnosis of drug eruption due to peplomycin was made.

Topics: Biopsy, Needle; Carcinoma, Squamous Cell; Drug Eruptions; Follow-Up Studies; Hand Dermatoses; Humans; Immunohistochemistry; Male; Middle Aged; Mouth Mucosa; Peplomycin; Prednisolone; Risk Assessment; Skin Diseases, Vesiculobullous; Skin Neoplasms; Stevens-Johnson Syndrome; Treatment Outcome

We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a 46-year-old man. Clinical staging was T3bN2M0. The patient received 50 Gy external radiation combined with intraarterial and systemic chemotherapy. Pathological complete response was found both in bladder and regional lymph nodes when he underwent radical cystectomy and lymph node dissection. The patient has been alive without evidence of disease for two years postoperatively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Radiotherapy Dosage; Urinary Bladder Neoplasms

The purposes of the present study were to analyze our experience with preoperative chemoradiotherapy followed by surgery for advanced tongue carcinoma and to assess the prognostic value of response to preoperative therapy in these tumors.. Between May 1988 and December 1999, a total of 43 patients with advanced but potentially resectable squamous cell carcinoma of the tongue were candidates for this study. A minimum tumor size of 3 cm was required. The mean age was 59.8 years (range, 26-85 years); 13 cases were advanced stage II, 23 cases were stage III, and 7 cases were stage IV. All patients were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy; 2-6 weeks later, they underwent curative surgery. Tumor regression rate, residual tumor grade, and histologic regression grade to the preoperative therapy were analyzed to determine their influence on the prognosis.. With a median follow-up of 60.5 months, overall survival rates were 86.0% for all cases, 92.3% for stage II cases, 77.3% for stage III cases, and 100% for stage IV cases. The progression-free survival rates according to tumor regression rate were 33.3% for group 1 (< 50% tumor regression), 66.7% for group 2 (> or = 50% and < 75% regression), 100% for group 3 (> or = 75% and < 100% regression), and 96.0% for group 4 (complete regression). The higher the tumor regression rates, the higher the survival rates. When patients who achieved a regression rate of 75% or higher were compared with those who did not, there was a significant difference in survival (P < .0001). The factors of residual tumor grade and histologic regression grade also had good correlations with the prognosis (residual tumor grade, P =.0324; histologic regression grade, P < .0001).. The findings of the present study suggest that response to preoperative chemoradiotherapy, such as tumor regression rate, residual tumor grade, and histologic regression grade, could be of prognostic value in patients with tongue carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Peplomycin; Preoperative Care; Prognosis; Radiotherapy, Adjuvant; Remission Induction; Retrospective Studies; Tongue Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase II as Topic; Disease-Free Survival; Female; Humans; Irinotecan; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Peplomycin; Uterine Cervical Neoplasms

Oral squamous carcinoma cell line SSCKN cells were shown to be highly sensitive to bleomycin, whereas SCCTF cells were minimally sensitive to this reagent. To determine whether the anticancer drug resistance to oral squamous carcinoma cells could be related to the degree of the drug-induced apoptosis, we examined the effects of peplomycin on induction of apoptosis in these cells. After reaching subconfluence, SCCKN and SCCTF cells were exposed to various concentrations of peplomycin. Peplomycin caused cytotoxicity in both SCCKN and SCCTF cells in a dose-dependent fashion with the maximal effect at concentrations of 1 and 10 microM, respectively, as determined by phase-contrast microscopy and WST-1 cell viability assay. By using the Hoechst 33342 staining, we observed marked nuclear condensation and fragmentation of chromatin in SCCKN cells treated with 1 microM peplomycin. However, SCCTF cells treated with 1 microM peplomycin showed neither nuclear condensation nor fragmentation. DNA ladder formation was also detected in both cell lines by treatment with peplomycin. The induced DNA ladder formation in SCCKN and SCCTF cells was dose-dependent, with the maximal effect at concentrations of 5 and 50 microM, respectively. Bleomycin also induced DNA ladder formation in SCCKN and SCCTF cells with different sensitivities. Mitomycin C induced DNA laddering in both SCCKN and SCCTF cells; however, the intensity of DNA ladder formation was almost the same in both cell lines. The present results indicate that peplomycin-induced apoptosis in oral squamous carcinoma cell lines depends on the sensitivity of these cells to bleomycin.

Topics: Antibiotics, Antineoplastic; Apoptosis; Bleomycin; Carcinoma, Squamous Cell; Colorimetry; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Microscopy, Phase-Contrast; Mitomycin; Mouth Neoplasms; Peplomycin; Treatment Outcome; Tumor Cells, Cultured

Using an orthotopic implantation model in which oral cancer invasion and metastasis can be reproduced, we investigated the inhibitory effects of anticancer agents on invasion and metastasis.. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19, was implanted into the oral floor of nude mice, and cisplatin or peplomycin was administered to the mice 7 or 14 days after implantation. The effects of each anticancer drug and different administration timings on cancer invasion and metastasis were investigated.. Tumor size and the ratio of proliferating cell nuclear antigen-positive cells was significantly reduced. In the control group, the tumors showed grade 4C mode of invasion, whereas in the groups treated with anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory effect on tumor invasion being observed. The rate of metastasis in the cervical lymph node was significantly decreased in the groups treated with the cisplatin or peplomycin on day 7 after implantation. The tumor stage progression in the metastatic lymph nodes was also inhibited.. Chemotherapy is effective not only for tumor diminution but also for inhibiting invasion and metastasis. In light of these effects, administration of anticancer drugs may be clinically useful in this regard.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line; Cisplatin; Disease Models, Animal; Drug Administration Schedule; Lymphatic Metastasis; Mice; Mice, Nude; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Peplomycin

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.

Topics: Animals; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cyclooxygenase 2; DNA, Complementary; Fluorouracil; Gamma Rays; Genetic Vectors; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Isoenzymes; Membrane Proteins; Mice; Mice, Nude; Neoplasm Transplantation; Oligonucleotides, Antisense; Peplomycin; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Time Factors; Transfection; Tumor Cells, Cultured; Up-Regulation

Squamous cell carcinoma (SCC) arising in the skeletal muscle is rare. A case of a 19-year-old female patient with an intramuscular forearm tumor showing a histopathologically overwhelming squamous element is presented. Microscopic examination revealed the classical features of SCC, including horn pearls, individual cell keratinization and intercellular bridge. A malignant spindle cell component was not detected. Neither evidence of another primary site nor skin lesion over the tumor was found and no metastatic lesion was detected in the 5 years since the appearance of the mass.

Topics: Actins; Adult; Antineoplastic Combined Chemotherapy Protocols; Axilla; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Therapy, Combination; Female; Forearm; Humans; Lymph Node Excision; Lymph Nodes; Magnetic Resonance Imaging; Mitomycin; Muscle Neoplasms; Oncogene Proteins, Fusion; Peplomycin; Radionuclide Imaging; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Treatment Outcome; Vincristine

Primary squamous cell carcinoma (SCC) is an uncommon tumor of the prostate gland. A 65-year old man complained of obstructive symptoms.. Transrectal palpation and diagnostic imaging indicated an ordinary adenocarcinoma, although serum prostate-specific antigen (PSA) was normal. Biopsy specimens revealed SCC with the serum SCC antigen elevated. The patient was treated with pelvic irradiation and systemic administration of cis-platinum and peplomycin, which resulted in shrinkage of the cancer.. No evidence of recurrence has been seen for 18 months.

Topics: Aged; Antibiotics, Antineoplastic; Biopsy; Carcinoma, Squamous Cell; Cisplatin; Humans; Magnetic Resonance Imaging; Male; Peplomycin; Prostatic Neoplasms; Radiation-Sensitizing Agents; Tomography, X-Ray Computed

Paraffin sections of biopsy specimens obtained from 46 patients with oral squamous cell carcinomas were stained with both anti-peptide antibody against human Fas antigen and monoclonal mouse antibody against human proliferating cell nuclear antigen (PCNA). The patients received chemotherapy with a combination of carboplatin and peplomycin sulfate or mitomycin C and peplomycin sulfate before surgery. The relation between the expression of Fas antigen and the clinical features of each case was examined. The correlation between PCNA and Fas antigen expression was also studied. The mean PCNA labeling index of the 22 Fas-negative cases was 46.9%, which was significantly higher than that of the 24 Fas-positive cases (39.5%). Strong correlations were found between the expression of Fas antigen and the response to chemotherapy, tumor recurrence, and survival. The Fas-negative group had only a minor response to chemotherapy and a poor outcome, whereas the Fas-positive group had a better response to chemotherapy and a good outcome. Although lymph node metastasis was significantly related to survival, there was no correlation between Fas antigen expression and lymph node metastasis. The Kaplan-Meier survival curve of patients positive for Fas antigen was significantly better than that of patients negative for Fas antigen. Our results suggest that Fas antigen expression is an independent predictor of outcome whose usefulness should be evaluated in prospective studies.

Topics: Actuarial Analysis; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; fas Receptor; Female; Humans; Immunohistochemistry; Logistic Models; Male; Middle Aged; Mitomycin; Mouth Neoplasms; Peplomycin; Proliferating Cell Nuclear Antigen; Treatment Outcome

Twenty-five patients with advanced cervical cancer (IIb-IVa) were treated with neoadjuvant chemotherapy followed by radical hysterectomy or radiotherapy. According to the evaluation by MRI, complete response was achieved in 2 cases and partial response in 17 cases. Eventually the response rate was 76%. The response rate was higher in squamous cell carcinomas (85%) than adenocarcinomas or adenosquamous carcinomas (67%). The histological effect is superior in squamous cell carcinomas than adenocarcinomas or adenosquamous carcinomas. Radical hysterectomy was performed in 5 cases of 11 (45%) stage III-IVa cervical cancers. There was no correlation between tumor size and response to NAC. NAC therapy may be useful therapy in advanced cervical cancers, especially squamous cell carcinomas.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Hysterectomy; Ifosfamide; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Staging; Peplomycin; Pilot Projects; Prognosis; Uterine Cervical Neoplasms; Vinblastine; Vincristine

The overall survival rate (OSR) of 36 patients with nasopharyngeal carcinomas (NPC) treated at Kyushu University hospital between 1983 to 1992 was analyzed. As primary treatment, 16 patients received a combination therapy of 5-fluorouracil, vitamin A, and radiation (FAR therapy); two patients received radiotherapy only; 18 patients received FAR therapy plus adjunctive systemic chemotherapy consisting of cisplatin and peplomycin. The radiation dose to the nasopharynx was 6000 to 7050 cGy while that to the neck was 4000-6000 cGy. The 5-year OSR of all the patients was 49%. Histological type (moderately differentiated squamous cell carcinoma) and patient age (> or = 55) were found to be significant prognostic factors for a worse OSR. Although survival decreased with increasing T stage, no significant difference was observed. The 5-year OSR of the patients treated with FAR therapy was 53% and was 51% with FAR therapy plus chemotherapy. Compared to FAR therapy alone, adjunctive chemotherapy did not increase OSR of the patients with NPC.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Humans; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Peplomycin; Retrospective Studies; Survival Rate; Vitamin A

We investigated the relationship between manganese superoxide dismutase (Mn-SOD) activity and apoptosis induced by anticancer drugs and radiation. Although the activity of copper, zinc-SOD did not differ greatly among 9 squamous cell carcinoma (SCC) cell lines (OSC-1 to OSC-9), the Mn-SOD activity did differ among the cell lines. The Mn-SOD activity was increased by treatments with 5-fluorouracil (5-FU), peplomycin and 137Cs, reaching plateau levels at 12 h after treatment and then decreasing gradually. When OSC-1 and OSC-3, and OSC-2 and OSC-4 were examined as representative cell lines with low and high Mn-SOD activity, respectively, the decrease was more prominent in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The intracellular levels of superoxide and hydrogen peroxide (H2O2) were increased after treatment with the anticancer agents, and the increases were larger in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The decrease of mitochondrial membrane potential (deltapsi(m)) by the anticancer agents was marked in OSC-1 and OSC-3. Correspondingly, the release of cytochrome c, the activation of caspase-3 and the cleavage of poly(ADP-ribose)polymerase were stronger in OSC-3 than in OSC-4. In addition, apoptosis induced by the anticancer agents was prominent in OSC-3, exhibiting a close relationship with the deltapsi(m) and the H2O2 level. These results indicate that Mn-SOD in SCC cells modulates apoptosis induction and the inactivation of Mn-SOD might be a promising strategy for SCC treatment.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Survival; Fluorouracil; Gamma Rays; Humans; Hydrogen Peroxide; Mice; Peplomycin; Superoxide Dismutase

The effects of an induction chemotherapy with THP-adriamycin, cisplatin, and peplomycin (TPP) were studied in 32 patients with operable oral cancer. The histological evaluation according to the Shimozato-Oboshi classification was Grade (G) IV in ten cases (31.3%), GIII in one case, and GIIb in four cases. Induction of apoptosis and differentiation-inducing effects, hyperkeratinization or bone formation, were observed in some cases. The overall clinical response rate and histological response rate were 63% and 47%, respectively. Grade III was obtained in seven metastatic lymph nodes of three patients. The expressions of PCNA, p53, and AgNORs before and after chemotherapy were studied. The prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors (GIII, IV) was significantly lower than that of the poorly responsive tumors (G0-IIb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P < 0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the efficacy of TPP chemotherapy.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cisplatin; Coloring Agents; Doxorubicin; Female; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Nucleolus Organizer Region; Osteogenesis; Peplomycin; Proliferating Cell Nuclear Antigen; Remission Induction; Silver; Treatment Outcome; Tumor Suppressor Protein p53

We assessed neoadjuvant intraarterial chemotherapy (NAC) followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer.. Over 5 years, 48 consecutive women with International Federation of Gynecology and Obstetrics stage IIb-IVa cervical cancer were enrolled. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (100 mg/m2, day 1) or carboplatin (400 mg/m2, day 1) and peplomycin (20 mg/m2, day 1) for two courses separated by 3 weeks. Doxorubicin (30 mg/m2, day 1) was added for patients with adenocarcinoma. Stage III patients who responded to NAC and Stage IIb patients underwent radical hysterectomy with pelvic lymphadenectomy. Stage III patients not responding to NAC and all stage IVa patients were treated with pelvic radiotherapy.. Complete response was achieved in 5 (10.4%) of 48 patients, while a partial response was noted in 32 (66. 7%) and stable disease in 11 (22.9%). Of 25 patients with stage IIIb disease, 16 (64.0%) were able to undergo surgery. The 4-year disease-free survival (DFS) was 80.0% in patients with stage IIb and 62.3% in patients with stage III. In stage IIIb, the 4-year DFS in patients receiving surgery (75.2%) was higher than the DFS for those receiving radiotherapy (44.4%) (P < 0.05). Grade 3 or 4 leukopenia developed in 17 (35.4%) patients. Nausea and vomiting of grade 2 or higher occurred in 34 (70.8%). Creatinine clearance transiently decreased (>/= grade 2) in 16.6%. Patients negative for serum squamous cell carcinoma-associated antigen (SCC) responded better to NAC than to SCC-positive cases, and SCC-negative survival was significantly better than SCC-positive survival (P < 0.05).. Neoadjuvant intraarterial chemotherapy with platinum was safely performed, and a survival benefit followed radical surgery with or without radiotherapy after response to NAC.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Doxorubicin; Female; Humans; Hysterectomy; Iliac Artery; Infusions, Intra-Arterial; Middle Aged; Peplomycin; Predictive Value of Tests; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms

To compare the efficacy of adjuvant chemotherapy after radical hysterectomy with that of adjuvant radiotherapy.. One hundred one women with invasive cervical carcinoma (stage IB through early stage IIB) underwent radical hysterectomy at Saga Medical School Hospital. Of these patients, 53 with squamous or adenosquamous carcinoma were classified as high risk, based on the presence of one or more of the following high-risk factors for recurrence: 1) lymph node metastasis, 2) deep cervical stromal invasion (greater than 3/4 thickness), and 3) parametrial invasion. Adjuvant chemotherapy with a combination of cis-diamminedichloroplatinum (CDDP), vincristine, mitomycin C, and peplomycin (POMP), was prescribed. The outcome was compared with that for 127 patients who were classified as high risk under the same criteria and who received adjuvant radiotherapy at Kyushu University Hospital.. The 5-year survival rates were much the same: 83.0% for adjuvant chemotherapy and 81.7% for adjuvant radiotherapy. In the chemotherapy group, intra- and extrapelvic recurrences accounted for 85 and 23% of all recurrences, respectively, whereas recurrences were noted for 38 and 71% in the radiotherapy group, respectively (P < .01).. The use of adjuvant chemotherapy reduces extrapelvic recurrences. The combination of both adjuvant therapies may improve the prognosis for high-risk patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Female; Follow-Up Studies; Humans; Hysterectomy; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Peplomycin; Prognosis; Radiotherapy, Adjuvant; Radiotherapy, High-Energy; Risk Factors; Survival Rate; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms; Vincristine

To investigate the role of laser hyperthermia in penis-conserving therapy for penile carcinoma.. Penile carcinoma KPK-1 cells were transplanted into nude mice to induce tumour; the effects of laser hyperthermia, the chemotherapeutic agent peplomycin, or their combination on the inhibition of KPK-1 tumour growth were assessed. In a clinical study, two patients with well-differentiated, stage T2 penile tumours with corporeal involvement were treated to conserve the penis using concurrent radiation, laser hyperthermia and peplomycin. They had no pathologically identified regional lymph node metastasis. Radiation was given for 5 days a week for 3 weeks at a total dose of 30 Gy. Nd:YAG laser hyperthermia was administered at 42-43 degrees C for 15 min twice a week for 3 weeks immediately after radiation. Peplomycin (10 mg per day) was administered intravenously over 24 h together with the laser hyperthermia.. The combined treatment with laser hyperthermia and peplomycin completely inhibited KPK-1 tumour growth, but the treatment with either laser hyperthermia or peplomycin alone had little effect. The results were also corroborated by the histopathological findings; the necrotic area in mice treated with combined therapy was much larger than that in those treated with laser hyperthermia alone. Both patients given combined laser hyperthermia, radiation and peplomycin were treated successfully, with the penis and sexual function conserved, and both survived for > 7 years with no evidence of any local or regional recurrence. There were no major complications related to the combined treatment.. This preliminary study showed that combined treatment with laser hyperthermia, radiation and peplomycin might be a promising therapy for conserving the penis in some patients with stage T2 penile tumours.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Humans; Hyperthermia, Induced; Laser Therapy; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Penile Neoplasms; Penis; Peplomycin

We investigated the expression of hMSH2, a human mutS homologue from chromosome 2p, in oral and oropharyngeal squamous cell carcinoma (SCC) by an immunohistochemical technique and performed tumor in vitro chemosensitivity testing. In 58 oral and oropharyngeal SCC, the hMSH2 positive score was inversely associated with tumor size, but not with other clinical parameters. Among five anticancer drugs (cisplatin (CDDP), 5-FU, peplomycin, mitomycin C and doxorubicin), only for CDDP was sensitivity to cytotoxicity correlated with the hMSH2 positive score. The susceptibility of hMSH2-positive tumors to CDDP killing was significantly higher than that of hMSH2-negative tumors. Immunohistochemical results regarding hMSH2 are promising in the evaluation of the sensitivity of cancer cells to CDDP cytotoxicity and enable one to select patients for adjuvant chemotherapy for oral and oropharyngeal SCC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; DNA-Binding Proteins; Doxorubicin; Female; Fluorouracil; Humans; Immunohistochemistry; Male; Middle Aged; Mitomycin; Mouth Neoplasms; MutS Homolog 2 Protein; Oropharyngeal Neoplasms; Peplomycin; Proto-Oncogene Proteins; Tumor Cells, Cultured

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40-100 mg peplomycin or 250-500 mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12-64 months after therapy, or they died without evidence of cancer 12-98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

Topics: Adenocarcinoma; Adsorption; Aged; Aged, 80 and over; Antineoplastic Agents; Carbon; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Injections, Intralesional; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Pilot Projects; Stomach Neoplasms; Survival Rate

In patients with head and neck carcinoma, fixed enlarged metastatic lymph nodes (LNs) are sometimes inoperable and carry an increased risk of mortality. To control metastatic LNs, we attempted intranodal injection of anticancer agents.. Fifteen patients with squamous cell carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or maxillary sinus (3) were enrolled. These patients consisted of two groups, those in the early era in which the fixed LNs of six patients were treated with 60Co (RA group) and those in the late era in which both radiation and intranodal injection of anticancer agents were administered to nine patients (IN group). Intranodal injection consisted of peplomycin, 5-fluorouracil, and cis-diamminedichloroplatinum.. In the IN group, LNs regressed from about 40% to nearly 100%, although two patients showed no appreciable response. The LNs treated by combination therapy regressed considerably while LNs in the same patients treated with 60Co alone showed a minor response or grew gradually. In three patients, the LNs regressed sufficiently to be extirpated safely. The good clinical response in the locally injected LNs was histologically associated with distinct evidence of tumor cell degeneration. In the RA group, none of the LNs responded to radiation with 60Co; one LN exhibited slight regression, but the others enlarged during and soon after the radiation. Compatible with the clinical effects, many patients in the IN group demonstrated a good prognosis; three are alive without disease, and four survived for prolonged periods. However, all patients in the RA group died due to progression of the positive LNs or pulmonary complication within 10 months.. These results indicate that intranodal injection of anticancer drugs is useful for the management of fixed enlarged LNs.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Injections, Intralymphatic; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Patient Selection; Peplomycin; Salivary Gland Neoplasms

An auxiliary method for determination of chemosensitivity with the subrenal capsule assay (SRCA) was developed in which the specific activity of succinate dehydrogenase (SD) of tumor implanted beneath the renal capsule is measured. The appropriate conditions for measuring the specific activity of SD were determined. The chemosensitivity of tumors, derived from six xenograft lines originating from oral squamous cell carcinomas, to peplomycin (PEP), cisplatin (CDDP), and 5-fluorouracil (5-FU) were evaluated by the SRCA and the nude mouse assay (NMA). The chemosensitivity evaluated by NMA displayed a higher degree of correlation with that determined by the improved SRCA than with that determined by the conventional SRCA. The correlations between overall accuracy of prediction with the NMA and those with the conventional SRCA and the improved SRCA were 72.2% and 88.9%, respectively. These findings suggest that our new assay may be useful for evaluation of chemosensitivity in the SRCA.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Colorimetry; Coloring Agents; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Neoplasm Transplantation; Peplomycin; Regression Analysis; Subrenal Capsule Assay; Succinate Dehydrogenase; Tetrazolium Salts; Thiazoles

Salivary polymorphonuclear leukocyte (SPMN) functions were examined in 18 patients with oral squamous cell carcinoma and in 20 healthy individuals. SPMN obtained from patients before therapy exhibited significantly less FMLP-stimulated chemotactic activity (132.4 +/- 17.5 cells/0.26 mm2) than that in SPMN from controls (177.1 +/- 11.6 cells/0.26 mm2), although no difference in phagocytosis was observed. When stimulated with PMA or FMLP, control SPMN generated superoxide (O2-) at levels of 50.3 +/- 10.5 pmol/min/10(4) cells and 88.4 +/- 15.4 pmol, respectively, while SPMN from untreated patients generated significantly reduced O2- in the presence of PMA or FMLP (24.3 +/- 3.5 pmol and 59.5 +/- 9.8 pmol, respectively). Only slightly lower chemiluminescence was observed in SPMN from untreated patients however, compared to controls, values being 68.0 +/- 18.9 vs 81.3 +/- 14.9 peak mV by PMA and 62.4 +/- 13.7 vs 64.4 +/- 12.9 peak mV by FMLP. Compared to Candida killing in control subjects (24.9 +/- 3.1%). SPMN from patients before treatment exhibited significantly reduced activity (18.7 +/- 4.9%). Further suppression of the SPMN functions examined was observed after chemoradio-therapy. Suppressed SPMN function in cancer patients, especially that associated with chemoradiotherapy, may therefore play a part in oral candidiasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Candidiasis, Oral; Carcinoma, Squamous Cell; Case-Control Studies; Chemotaxis, Leukocyte; Cobalt Radioisotopes; Combined Modality Therapy; Cranial Irradiation; Cytotoxicity, Immunologic; Female; Fluorouracil; Humans; Leukocyte Count; Luminescent Measurements; Male; Middle Aged; Mouth Neoplasms; Neutrophils; Peplomycin; Phagocytosis; Remission Induction; Respiratory Burst; Saliva; Superoxides

Induction chemotherapy, followed by definitive treatment, was performed in patients with advanced squamous-cell carcinoma of the head and neck. In this study, carried out between 1984 and 1991, testing the effectiveness of multimodality therapy in patients with previously untreated advanced (stage III and IV) squamous-cell carcinoma of the pharynx, patients received two different induction chemotherapy regimens: cisplatin, vincristine (Oncovin) plus peplomycin (COP), and cisplatin plus continuous 120-hr 5-fluorouracil (5-FU) infusion (CF) for two courses. Overall response rates (complete response plus partial response) to each of the two induction chemotherapy regimens were high: 76 and 82%, respectively. Superior complete response rate in the group receiving CF therapy was 16% versus 10% for COP therapy. Responders to induction chemotherapy had significantly better survival compared with non-responders. The toxicity of these two regimens was tolerable and manageable. It is indispensable to develop the more efficacious chemotherapy regimen with the potential to induce complete disappearance of tumors in patients with advanced head and neck carcinomas.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Cisplatin; Female; Fluorouracil; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Staging; Peplomycin; Pharyngeal Neoplasms; Pharynx; Retrospective Studies; Treatment Outcome; Vincristine

A group study of chemotherapy for head and neck squamous cell carcinoma, using CDDP, THP and PEP, was carried out on 32 cases at the department of Otolaryngology, University of Tokyo, and 7 affiliated hospitals. The combined chemotherapy, which we call "PTP therapy", consisted of 30 mg/m2 of THP on day 1, 70 mg/m2 of CDDP on day 2, and 5 mg/body/day of PEP on 4 successive days. The overall response rate was 78.1% (CR: 15.6%; PR: 62.5%). No major side effect was observed in any case. PTP therapy is useful in neoadjuvant chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Fosfomycin; Head and Neck Neoplasms; Humans; Male; Metoclopramide; Middle Aged; Peplomycin

To study the alteration of nuclear DNA content of cancer cells after peplomycin (PEP) treatment, DNA cytofluorometry was performed in combination with 3H-thymidine (3H-TdR) autoradiography using cultured A431 cells. The cells in the logarithmic growth were treated with PEP (1.25 micrograms/ml) for 24 hr, during the first 4 hr of which they were pulse-labeled with 3H-TdR (2.4 x 10(4) Bq/ml). After washing with PBS, the cells were then cultured without both PEP and 3H-TdR, fixed at different times and stained with propidium iodide (PI) for the auto-stage cytofluorometry, which enabled DNA content analysis for labeled and unlabeled cells by repeated scanning of the same cell population. The nuclear DNA content histograms demonstrated that A431 cells were mostly arrested in G2 phase of 4C stem line by treatment with PEP for 24 hr. This G2 block lasted up to 8 hr after removal of the drug, and thereafter, marked polyploidization associated with DNA synthesis occurred, showing almost no mitotic figures, while only a few cells returned to G1 phase via M phase. During the period of 72-120 hr, however, the fractions of advanced polyploid cells (DNA content > or = 8C) gradually decreased and the DNA content distribution pattern became eventually similar to the original one as seen before PEP treatment. From these results we hypothesized as follows: 1) At S-G2 boundary, there is some control mechanism that checks whether the cells, after S phase, can enter the M phase or not. 2) The cells, which are not permitted to enter mitosis by the control mechanism, show marked polyploidization. 3) Only the cells that enter into mitosis can live and proliferate, though the advanced polyploid cells die shortly. 4) This control mechanism might be related to the precision of DNA repair that is checked at the G2-M checkpoint.

Topics: Autoradiography; Carcinoma, Squamous Cell; Cell Division; DNA Repair; DNA, Neoplasm; Flow Cytometry; G2 Phase; Humans; Peplomycin

We produced two types of murine monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitative diagnosis and optimum therapy. The isotypes of KYSM-1 and KIS-1 were IgM and IgG1, respectively. Immunohistochemical staining demonstrated that both antibodies strongly reacted with human carcinoma cell lines of the esophagus, lung and oral cavity. Fluorescence activated cell sorter analysis demonstrated that each antigen of KYSM-1 and KIS-1 exposed to cellular membrane of squamous carcinoma cells and molecular weights of these antigens detected by KYSM-1 and KIS-1 were 60 kDa and 90 kDa, respectively, in non-reduced condition. These 2 monoclonal antibodies were labeled with 125I by the Iodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus. Regarding in vivo accumulation of 125I-labeled antibodies, however, KIS-1 alone showed significantly high values in the tumor at 5 and 7 days after the injection. From this result, KIS-1 was labeled with 131I and injected into the tumor-bearing mice with a dose of 200 microCi. Moderately effective results were found in the tumor by 14 days after the injection. Furthermore, KIS-1 was also conjugated to peplomycin (PEP). In in vitro and in vivo effects of targeting chemotherapy, the conjugates killed human squamous carcinoma cells and tumor-implanted nude mice. These results suggest that the 131I-labeled KIS-1 and/or KIS-1-PEP conjugate may provide a targeting therapy in patients with squamous cell carcinoma of the esophagus.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunotoxins; Mice; Mice, Nude; Neoplasm Transplantation; Peplomycin

Activated carbon particle adsorbed-peplomycin (PEP-CH) was administered to three patients who had advanced esophageal cancer and its clinical usefulness was evaluated. The PEP-CH was injected endoscopically into the tumor or the adjacent normal esophageal tissue. Case 1 and case 3 were treated by topical injection of PEP-CH with or without surgery and case 2 was subjected to the PEP-CH treatment with radiation. The barium swallow and endoscopic examination exhibited a marked tumor reduction in all the patients at the end of the PEP-CH treatment. Although a marked clinical response was seen, case 1 died of postoperative complication. Two patients were capable of oral food intake after the treatment, which had been impossible before the treatment. There were no serious adverse side effects caused by the PEP-CH treatment in all the patients. PEP-CH should prove valuable as a new form of chemotherapy for the treatment of esophageal cancer patients.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carbon; Carcinoma, Squamous Cell; Drug Carriers; Esophageal Neoplasms; Esophagoscopy; Humans; Male; Middle Aged; Peplomycin; Pilot Projects

A new drug-delivery format comprising activated carbon particles adsorbing peplomycin (PEP-CH) was developed for the treatment of superficial esophageal cancer.. The drug distribution was measured in rats that received subcutaneous injections of PEP-CH or peplomycin aqueous solution. In 6 patients with superficial esophageal cancer, peplomycin as PEP-CH, 5-10 mg once a week for 4-10 weeks (total, 40-100 mg/patient) was injected endoscopically into primary lesions.. Rats given PEP-CH had significantly higher peplomycin levels in the regional lymph nodes and the injection site than rats given aqueous solution. Five patients have survived to the present or died without cancer after 27-72 months. The remaining patient has survived without cancer for 8 months after a second course of PEP-CH against recurrence.. PEP-CH therapy seems to have a good therapeutic effect on superficial esophageal cancer, although the present clinical study may have been biased by patient selection.

Topics: Aged; Aged, 80 and over; Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Endoscopy; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Injections; Lymph Nodes; Male; Middle Aged; Peplomycin; Pilot Projects; Rats; Rats, Inbred Strains; Tissue Distribution

Preoperative 5-drug-combined intraarterial infusion chemotherapy using carboplatin as a main component was performed in a case of uterine cervical squamous cell carcinoma of Stage IIa. The regimen employed was as follows: carboplatin (100 mg/m2) on Day 4 and 5, vincristine (0.6 mg/m2) on Day 1, peplomycin (5 mg/body) on Day 1, 2, and 3, methotrexate (5 mg/m2) on Day 2 and 3, and doxorubicin (15 mg/m2) on Day 4. These drugs were administered into the right inguinal region through a residual catheter at 3-week intervals prior to operation. After completion of 3 courses, the patient achieved a CR confirmed by pathological analysis and diagnostic imaging followed by extended radical hysterectomy. Side effects observed, especially renal disturbance and myelosuppression, were all tolerable. Intraarterial infusion chemotherapy using carboplatin was thus suggested to be useful against malignant tumors in the gynecological field.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Doxorubicin; Drug Administration Schedule; Female; Humans; Hysterectomy; Infusions, Intra-Arterial; Methotrexate; Middle Aged; Peplomycin; Preoperative Care; Remission Induction; Uterine Cervical Neoplasms; Vincristine

Twenty seven patients with cervical cancer were treated with PVP therapy including cisplatin 50mg/m2, vinblastine 4mg/m2 and peplomycin 15mg/body during the period from 1984 to 1989. Fourteen patients had a primary lesion. Five of 14 patients were treated with PVP as the primary therapy because of pathological findings which suggested no radiotherapy effect. Nine patients had a radio-resistant lesion and were treated following PVP. Twelve of 14 cases responded and median survival time was 32.5 months (2-101 months). Thirteen patients were treated with PVP because of recurrent cervical cancer. Five of those which recurred after radiotherapy and other 8 cases had been treated with radical hysterectomy and radiotherapy. Two of 5 cases with previous radiotherapy responded and one of 2 patient is still alive with no evidence of disease, but the patients treated with radical hysterectomy and pelvic irradiation showed no sign of a PVP effect and all of them died within 1 year. Primary cases responded even after radiation and some are still alive after more than 5 years. But PVP had no effect on the in patients which there was recurrence. It is necessary to determine which regimen is better, how to select the dose of cisplatin and how to combine the chemotherapy and other therapy. Patients who responded survived for a long time and PVP is an effective therapy. To obtain a better prognosis for advanced cervical cancer, we need a prospective randomized study of radio-chemotherapy or chemo-radiotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Middle Aged; Peplomycin; Survival Rate; Uterine Cervical Neoplasms; Vinblastine

In Japan the regimen with peplomycin has been mainly used for the treatment of squamous cell carcinoma (SCC). But recently, a regimen with cisplatin, particularly the combination of cisplatin and adriamycin (CA chemotherapy) has been used for the treatment of SCC, and a better prognosis has resulted Since CA chemotherapy is very effective for not only SCC, but also basal cell carcinoma (BCC), we think it is a prominent neoadjuvant therapy for SCC and BCC. We have used CA chemotherapy for multiple lung metastasis of BCC over the past six years, and three times PR was obtained, with survival so far.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Skin Neoplasms

We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Peplomycin; Picibanil; Postoperative Period

Seventeen patients with bladder cancer were treated with semiselective intraarterial COMPA chemotherapy. One course of COMPA consisted of 20 mg/m2 cis-diammine-dichloroplatinum (CDDP) on days 4 and 5, 0.6 mg/m2 vincristine (VCR) (Oncovin) on days 1 and 2, 5 mg/m2 methotrexate (MTX) on days 2 and 3, 5 mg/body peplomycin (PEP) on days 1, 2 and 3, and 15 mg/m2 adriamycin (ADM) on day 4. These drugs were injected every 2 or 3 weeks through a polyurethane catheter the tip of which was placed just proximal to the aortic bifurcation and during injection both thighs were tied with a pressure of over 250 mmHg. From 2 to 6 courses (mean, 4.4 courses) were administered. Of the 17 patients, 4 achieved complete remission, 10 achieved partial remission and 3 showed no change. After this COMPA chemotherapy eight patients were able to retain their bladders while seven underwent immediate radical cystectomy. The adjuvant COMPA chemotherapy for two patients with pelvic metastasis after radical cystectomy showed good results. Mild degrees of anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, leukopenia and intestinal paralysis were observed. Instrumental troubles were seen in two cases; one involved dislocation of the tip of the catheter, the other was infection of the reservoir. Intraarterial COMPA chemotherapy is effective for neoadjuvant therapy of invasive bladder cancer, bladder-preserving treatment and adjuvant therapy of pelvic metastasis.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Male; Methotrexate; Middle Aged; Peplomycin; Urinary Bladder Neoplasms; Vincristine

It may not show accurate results if subrenal capsule assay (SRCA) is made only by measuring tumor size, because of infiltration of host inflammation cells resulted from host immune reaction. We developed a new method which make possible an accurate determination of chemosensitivity by measuring specific activity of succinate dehydrogenase (SD) of the tumor cells implanted in the subrenal capsular space. With reference to SDI test, the assay condition for measuring specific activity of SD was determined. A comparative study was carried out in which malignant tumors of the oral cavity serially transplanted in nude mice were tested with SRCA and subcutaneous transplantation assay in nude mice. Chemosensitivity to peplomycin (PEP), CDDP and 5-fluorouracil (5-FU) evaluated SSDI method and nude mouse assay showed a high correlation than those evaluated by TGIR method and nude mouse assay. The overall predictive accuracy compared with nude mouse assay was 72.2% by TGIR method and 88.9% by SSDI method. SSDI method seemed to be a useful method to evaluate the chemosensitivity in SRCA.

Topics: Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Fluorouracil; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Peplomycin; Subrenal Capsule Assay; Succinate Dehydrogenase; Tumor Cells, Cultured

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Screening Assays, Antitumor; Etoposide; Fluorouracil; Head and Neck Neoplasms; Humans; Methotrexate; Peplomycin; Tumor Cells, Cultured; Vincristine

Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell kinetics were studied both in vitro and in vivo with the aid of flow cytometry (FCM). Double staining with propidium iodide (PI) and fluorescein isothiocyanate (FITC)-labeled bromodeoxyuridine (BrdU) was used to analyze the cell cycle, and the number of viable cells was determined with fluorescein diacetate (FDA). Effects of combining the 2 agents were also studied to establish the most effective method of combination therapy. Furthermore, these agents were tried clinically on the basis of experimental results. Results showed that CDDP exerted its action at the S and G2M phases in the cell cycle and PEP at the G2M phase. Among the combination regimens in the experiments with CDDP, PEP, and CDDP + PEP as analyzed by FCM, the strongest block on the G2M phase was shown in the one at a 2-day interval, resulting in the most effective killing of the tumor cells. Clinical trial of the combination therapy showed the same results as the in vitro experiment; the therapy proved useful for improving the patient's clinical condition and the results obtained with CT imaging and pathology.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bromodeoxyuridine; Carcinoma, Squamous Cell; Cell Cycle; Cisplatin; Flow Cytometry; G2 Phase; Humans; In Vitro Techniques; Male; Maxillary Neoplasms; Middle Aged; Peplomycin; S Phase; Tumor Cells, Cultured

From favorable results with 254-S, a new cisplatin analogue, single administration, we have conducted a clinical study to investigate the efficacy of combination of 254-S, ifosfamide and peplomycin, each of which has a different dose limiting factor. A total of 45 patients, including 22 patients with stage III and IV cervical cancer and 23 cases with recurrent cervical cancer, were treated with at least two courses of 254-S (100mg/m2, iv. Day 1), ifosfamide (1,500mg/body, iv. Day 1-5) and peplomycin (5mg/body, im. Day 1-6), and tumor response was evaluated clinically and by CT scanning. The response rate obtained in patients with advanced disease was 81.8% (PR = 17, CR = 1) and that in cases with recurrence was 60.9% (PR = 12, CR = 2). Myelosuppression was the dose limiting factor. In the 121 courses, grade 3 and 4 of leucopenia and thrombocytopenia were observed with an incidence of 44% and 32%, respectively and DIC occurred in 3 cases with poor PS though they recovered after reducing the 254-S dose to 80 mg/m2. The other toxicities were mild except for alopecia. Anaphylaxia was observed in a case at the second administration though the patient recovered in 15 minutes. There was no death. As to prognosis, a significant prolongation of survival period was observed in recurrent cases and 4 cases are alive (NED) after one and a half year. In the advanced cases, until now 3 cases of stage IV have died from the disease. We have concluded that this regimen is effective as a neoadjuvant chemotherapy for advanced cervical cancer and useful for the treatment of recurrent cervical cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Ifosfamide; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Peplomycin; Prognosis; Uterine Cervical Neoplasms

The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma. The day-to-day changes in 10 carcinoma cases were evaluated for 9 days. The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased. The host reaction was recognized histologically from the 3rd or 4th day to the 9th day. However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day. The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day. In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable. 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%). Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Female; Fluorouracil; Humans; Immunohistochemistry; Mice; Middle Aged; Neoplasm Transplantation; Organoplatinum Compounds; Peplomycin; Subrenal Capsule Assay; Time Factors; Vindesine

In patients in whom cancer originating from a bed-sore has advanced to a stage where radical treatment is impossible, topical treatment with ointment, or systemic anti-cancer chemotherapy, is usually applied. We recently attempted treatment of extensive squamous cell carcinoma of the buttocks, for which radical treatment was impossible, by chemotherapy using a reservoir for intraarterial injection. This therapy involved intraarterial injection of bleomycin and 5-FU, together with topical treatment with 5-FU ointment. We describe the problems encountered with this therapy, e.g., measures against fever after intraarterial injection, management of the affected area, evacuation, possibility and limits of radiation therapy, and assessment of its efficacy.

Topics: Administration, Topical; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Buttocks; Carcinoma, Squamous Cell; Fluorouracil; Humans; Infusion Pumps; Infusions, Intra-Arterial; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Ointments; Peplomycin; Skin Neoplasms

We report a case of recurrent squamous cell carcinoma of the renal pelvis. A 61-year-old woman was readmitted to our hospital 4 months after left nephrectomy. The medical imaging method revealed a left retroperitoneal tumor and squamous cell carcinoma related antigen (SCC-Ag) elevated (82 ng/ml). We suspected a recurrent tumor from renal pelvic cancer. She received 2 courses of systemic chemotherapy with 5-FU and CDDP, but the tumor did not change. As a second treatment, combined radiotherapy with PEP was given. The tumor was reduced and SCC-Ag returned to the normal level. The patient is alive with no recurrence or metastasis at one year following these therapies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Kidney Calculi; Kidney Neoplasms; Kidney Pelvis; Middle Aged; Neoplasm Recurrence, Local; Peplomycin

Intra-arterial chemotherapy from bilateral superficial temporal arteries and radiotherapy were carried out preoperatively on two patients with oral cancer on the midline. Total doses of preoperative chemo- and radio-therapies were 160 mg/m2 of carboplatin, 50 mg of peplomycin and 20 Gy of 60Co-irradiation, respectively. Therapeutic effect of preoperative chemo- and radio-therapies was evaluated on the resected materials from histological point of view. In case 1, the effect was judged as Grade II A in Oboshi's classification, which indicated a mild destruction of architecture of tumor tissue and a few viable tumor cells, but an extreme reduction of the primary lesion was observed on clinical appearance. In case 2, the therapeutic effect was regarded as Grade II B, which indicated a severe destruction of architecture of tumor tissue and few viable tumor cells. Concerning toxicity, mucositis and slight thrombocytopenia (96,000/mm3) in case 1, and mucositis and leukopenia (2,300/mm3) in case 2 appeared. However, they soon recovered after termination of the preoperative therapies. From the above results, it was considered that a combination of bilateral intra-arterial chemotherapy and radiotherapy was quite effective as a preoperative treatment for oral cancers on the midline at the same doses of anti-neoplastic agents and irradiation as for the other unilateral oral cancers.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Cobalt Radioisotopes; Combined Modality Therapy; Humans; Injections, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Peplomycin

We performed hyperthermia concomitantly with the use of anticancer agents (etoposide and peplomycin) for the treatment of 13 patients with prostatic cancer. Seven of them were new cases and the others were recurrent ones. After intravenous administration of etoposide and peplomycin, hyperthermia was applied twice a week for 10 times in total. Clinical efficiency was evaluated by CT, ultrasound, prostatic biopsy. Tumor regression were observed in 12 cases. According to the General Rule for Clinical and Pathological Studies on Prostatic Cancer by Japanese Urological Association and the Japanese Pathological Society, one case of Ef2 and 5 cases of Ef1 were obtained with this treatment. Side effects caused by hyperthermia were urethral pain (1 case) and skin burning (1 case) noted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Bleomycin; Carcinoma, Squamous Cell; Drug Administration Schedule; Etoposide; Evaluation Studies as Topic; Humans; Hyperthermia, Induced; Male; Middle Aged; Peplomycin; Prostatic Neoplasms

A case of invasive pure squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy in a 79-year-old female is reported. Clinical staging of the tumor was T3b. We used combination chemotherapy with methotrexate, peplomycin and cis-platinum (MBD regimen) before radical cystectomy. Remarkable regression of the tumor was identified by computed tomographic scan after one course of chemotherapy and the surgical specimen revealed no viable tumors. The patient has been very active in her daily life without evidence of local recurrence or metastasis for more than one year. Squamous cell carcinoma of the bladder generally is regarded as having a poor prognosis with 5-year survival rates ranging from 7.4 to 26% and effective chemotherapy has not yet been established. Our experience suggests that the cure rate of pure squamous cell carcinoma may be improved markedly by the use of MBD regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cystectomy; Female; Humans; Methotrexate; Peplomycin; Remission Induction; Urinary Bladder Neoplasms

The present study evaluated the degree of renal impairment caused by intra-arterial hypertensive chemotherapy (CDDP, PEP). In 11 cases of advanced cancer of the uterine cervix, serum and urinary levels of alpha 1-microglobulin (alpha 1-m) and beta 2-microglobulin (beta 2-m), and urinary albumin (Alb) and lysozyme (LZM) were determined before the chemotherapy and 1,2 and 3 weeks after the therapy. Results are summarized as follows: 1. After intra-arterial chemotherapy, the histological classification was Grade I in 1 case (9.1%), Grade IIa in 2 cases (18.2%), and Grade IIb in 8 cases (72.7%). 2. Serum alpha 1-m and beta 2-m levels remained within the normal range after chemotherapy. 3. Urinary alpha 1-m, beta 2-m and LZM levels exceeded the normal limit between 1 and 2 weeks after the therapy, but thereafter they returned to normal. 4. Urinary Alb was significantly increased (p less than 0.05) between 1 and 2 weeks after therapy, but thereafter it returned to normal. These results suggested that intra-arterial chemotherapy (CDDP 100mg and PEP 40 mg in a dose) was effective for advanced cancer of the cervix and that renal disorders including tubular and glomerular impairment, which are the adverse effects of the therapy, were mild and reversible.

Topics: Adult; Aged; Albuminuria; Alpha-Globulins; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Bleomycin; Blood Pressure; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Infusions, Intra-Arterial; Kidney; Middle Aged; Muramidase; Peplomycin; Uterine Cervical Neoplasms

Chromosome findings in cultured skin fibroblasts from a patient treated with an anti-cancer drug, pepleomycin sulfate, for his penis cancer are reported. In two batches of specimens (days 16 and 34, respectively), out of 120 cells examined, a total of 26 abnormal cells (21.7%) were found with no common chromosome abnormalities; there were no clones. This cytogenetic pattern of abnormalities without clones in cultured skin fibroblasts differs from that seen in congenital disease or radiation-exposed skin fibroblasts. It is suggested that the anti-cancer agent is the most likely etiological factor for these uncloned chromosome abnormalities in cultured skin fibroblasts.

Topics: Bleomycin; Carcinoma, Squamous Cell; Cells, Cultured; Chromosome Aberrations; Fibroblasts; Humans; Male; Middle Aged; Penile Neoplasms; Peplomycin; Skin

In order to investigate the effect of an antisquamous cell carcinoma drug, peplomycin, the new analogue of bleomycin, on the production of a squamous cell carcinoma-associated tumor marker termed "SCC" (or TA-4), we carried out in vitro and in vivo experiments using the uterine cervical epidermoid cancer cell line SKG-IIIa, together with the investigation of the effect of sodium butyrate which was reported to be one of the representative gene modulators. In vitro production of SCC was biochemically and immunocytochemically confirmed in SKG-IIIa cells. Immunocytochemistry using anti-SCC antibody revealed that the total number of SCC-positive cells increased after the treatment with peplomycin (1.6 fold) or sodium butyrate (1.5 fold). The total amount of SCC in cultured medium, intracellular SCC, and cell debris during 5 days of culturation also increased with peplomycin (1.8 fold) and sodium butyrate (1.4 fold). These data strongly suggest that SCC production of SKG-IIIa cells is stimulated by peplomycin and sodium butyrate in vitro. In vivo experiments were also performed by administering peplomycin to nude rats with heterotransplanted tumors of SKG-IIIa, and transient elevations of serum SCC level (113% to 238% of the initial values) were observed, suggesting that SCC production of cancer cells is also stimulated by peplomycin in vivo.

Topics: Animals; Antigens, Neoplasm; Bleomycin; Butyrates; Butyric Acid; Carcinoma, Squamous Cell; Female; Humans; Male; Peplomycin; Rats; Rats, Nude; Serpins; Tumor Cells, Cultured; Uterine Cervical Neoplasms

From 1981 to 1987, 26 patients with oral malignancies, previously untreated squamous cell carcinomas, were treated by chemoradiation therapy, which consisted of Linac irradiation (2 Gy/d) under continuous intraarterial administration of 1.6 mg/d peplomycin (PEP). Twenty of these 26 patients did not undergo resection of the primary sites during initial hospitalization. Radicality of the PEP chemoradiation therapy was assessed after a long-term follow-up. Patients of Stage I to IV numbered 4, 7, 1 and 8, respectively. Total dosage was 60 Gy of Linac irradiation under 80-110 mg infusion of PEP. Overall CR rate and actuarial 5-year-survival rate were 75% and 63%, respectively, while these rates were 92% and 83%, respectively, for the Stage I to III cases, but 50% and 29%, respectively, for the Stage IV patients. Actuarial 5-year-survival rate of the CR Stage I to III cases was 91%, significantly higher than that of Stage IV cases (66%). We conclude the following: (1) This treatment is not indicative for patients with only a limited evaluation of PR available in the early stage of the therapeutic course. (2) Limited or uncertain response might occur in Stage IV cases. (3) The prognosis for the great majority of Stage I to III patients, however, is excellent.

Topics: Adult; Aged; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Feasibility Studies; Female; Follow-Up Studies; Humans; Infusions, Intra-Arterial; Male; Mouth Neoplasms; Peplomycin; Prognosis; Radiotherapy Dosage; Survival Rate

A 77-year-old man with recurrent lung cancer was administered peplomycin (PEP) 15 mg 1A only one time, from a link in the chain of chemotherapy. But just after it was occurred dyspnea, and heard crepitus by auscultation. And it was recognized of ground glass appearance and air-bronchogram in the entire lung field by chest X-ray photograph, so made a diagnosis of acute diffuse interstitial pneumonia by clinical. He died two days after in spite of emergency treatment, that is high dose steroid, O2 flow etc. We discussed the acute pulmonary side effect of peplomycin which is one of the carcinostatic antibiotic, according to this clinical progress.

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Peplomycin; Pulmonary Fibrosis

Topics: Bleomycin; Carcinoma, Squamous Cell; Cheek; Combined Modality Therapy; Humans; Hyperthermia, Induced; Mouth Mucosa; Mouth Neoplasms; Peplomycin

To determine the effect of continuous subcutaneous infusion of peplomycin on both antitumor activity and pulmonary toxicity, thirty-two patients with previously untreated oral squamous carcinoma were given peplomycin via osmotic microinfusion pump (SP-5, Nipro Co., Ltd.) at a daily dose of 5.0 mg subcutaneously. The mean dosage of peplomycin given was 79.8 mg. An overall response rate of 62.5% was achieved, with 21.9% complete response, and 40.6% partial response. The maximum reduction of tumor volume for responder could be generally observed when peplomycin was given at about 60 mg continuously. The most frequently encountered toxicity was a mucocutaneous reaction, manifested by stomatitis (34.4%) and skin eruption (18.8%), but they were mild and tolerable. A local skin reaction also occurred at the site of drug injection, and an ulcer formation developed in 12.5% of patients. Monitoring of pulmonary function by means of PaO2 revealed that 32.0% of patients had a decrease over 10% after peplomycin administration. However, interstitial pneumonitis eventually occurred in only one patient (3.1%). In conclusion, the regimen of continuous infusion of peplomycin is a useful method to administer peplomycin safely without reducing the antitumor effect compared to conventional intermittent injection.

Topics: Adult; Aged; Bleomycin; Carcinoma, Squamous Cell; Drug Eruptions; Female; Humans; Infusion Pumps; Infusions, Parenteral; Lung; Male; Middle Aged; Mouth Neoplasms; Oxygen; Partial Pressure; Peplomycin; Pulmonary Fibrosis; Remission Induction; Skin; Skin Ulcer; Stomatitis

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin

From 1977 to 1988, 61 patients have received radical treatment for a carcinoma of the mobile tongue. Fifty-nine of these patients were treated in association with a BLM (or PEP), and 26 patients with external irradiation. The local tumor control rate at two years was 77%, and subsequent lymph node metastasis was 25%. The five year cumulative survival rate was 55% and the main causes of death were found to be regional node metastases and other related diseases particularly. The determinate survival for TxN0 tumors was 83%. Six percent and 26% had radio-osteonecrosis and soft tissue necrosis respectively and three patients required surgery.

Topics: Adult; Aged; Aged, 80 and over; Bleomycin; Brachytherapy; Carcinoma, Squamous Cell; Combined Modality Therapy; Evaluation Studies as Topic; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Osteoradionecrosis; Peplomycin; Radiation Injuries; Remission Induction; Tongue Neoplasms

The long-term results and the preservation rate of maxillo-facial functions and structures were reviewed in 250 cases of maxillary sinus carcinoma which were treated at the Department of Otolaryngology of Keio University Hospital from 1957 to 1987, dividing them into 4 groups according to treatment modalities. The major treatment modalities of each group are as follows. I (1957-1966): Half of the cases underwent radical resection of the maxillo-facial region with or without postoperative irradiation. Preoperative intra-arterial chemotherapy was first introduced in 1963. II (1967-1973): Half of the cases received preoperative intra-arterial chemotherapy with bleomycin (BLM). III (1974-1981): The major treatment modalities consist of BLM ia + radiation----surgery and 5-FU ia + radiation. IV (1982-1987): Multidisciplinary treatment incorporating intra-arterial neoadjuvant chemotherapy mainly with cisplatin and peplomycin was performed. The 5-year survival rates of each group are as follows. I: 22%, II: 40%, III: 42%, IV: 55%. The 5-year survival rate was as high as 52% in cases treated with BLM ia followed by surgery in group II, but all cases underwent total maxillectomy. Meanwhile, in group IV, the 5-year survival rate was not only as high as 55%, but also the rate of total maxillectomy was quite low (18%). From these results, we realized that intra-arterial chemotherapy played an important role for improving the long-term results and preserving the functions and structures in the treatment of maxillary sinus carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Male; Maxillary Sinus Neoplasms; Middle Aged; Paranasal Sinus Neoplasms; Peplomycin

We have been treating advanced cancer of the uterine cervix with intra-arterial cisplatin (CDDP) and pepleomycin (PEP) (injected into the bilateral internal iliac artery), combined with radiotherapy and hysterectomy. Concomitant angiotensin II (AT II) administered by intravenous drip infusion was double the tumoral blood flow and thereby enhanced the efficiency of the intra-arterial chemotherapeutic regimen. But CDDP runs the risk of renal and myelotoxicity, so we studied renal dysfunction after treatment by examining serum and urinary beta 2-microglobulin (beta 2-m), and RBC, Hb, WBC, lymphocyte, and PLT.. At 1 week after the treatment, evaluation of the histological effects showed, Grade IIb: 72.7% (8/11 cases). Serum beta 2-m was within normal limit and not changed. Urinary beta 2-m levels increased to abnormal levels at 1 and 2 weeks after treatment, and fell to normal levels at 3 weeks after treatment. RBC, Hb, WBC, lymphocyte, and PLT fell most at 3 weeks after treatment and then increased slowly. This suggests that hypertensive intra-arterial chemotherapy (CDDP) impaired kidney and bone marrow, mildly and reversibly, and its appropriate interval is about 4 weeks.

Topics: Adult; Aged; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Pressure; Bone Marrow; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Depression, Chemical; Drug Evaluation; Female; Humans; Infusions, Intra-Arterial; Kidney; Middle Aged; Peplomycin; Uterine Cervical Neoplasms

Selective intra arterial hypertensive infusion of CDDP (100 mg) and PEP (40 mg) with angiotensin II was performed in a 64 year-old housewife with inoperable uterine cervical cancer stage IVa and transitional cell cancer of bladder (grade 1-2). PEP at 5 mg/day was also administered for 20 days (total 100 mg) using an implanted Drug Delivery System through the left internal iliac artery combined with irradiation therapy. There were hardly any side effects due to this treatment except for a slight upper digestive tract disturbance and bone marrow suppression, and the cancerous lesion gradually regressed following this treatment. This case suggested the efficacy of intra-arterial infusion using an implanted Drug Delivery System for advanced uterine cervical cancer. There has been no sign of recurrence six months after this treatment.

Topics: Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Infusion Pumps; Infusions, Intra-Arterial; Middle Aged; Neoplasms, Multiple Primary; Peplomycin; Remission Induction; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Multi-drug chemotherapy containing cisplatin has been reported to be one of the most active chemotherapy regimens in advanced or recurrent head and neck squamous cell carcinoma. In this study, the current status of clinical investigation of combination chemotherapies is reviewed. And our data are presented in head and neck cancer with multi-drug chemotherapy containing cisplatin. Thirty-five patients of stage 3-4 and 70 patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated by multi-drug chemotherapy containing cisplatin, and radiotherapy and/or operation. The overall response rate was 71.4%, with 17.1% complete remission in previously untreated, locally advanced patients and 31.4% in recurrent or metastatic patients. Problems of chemotherapy combined with radiotherapy and future direction of clinical study in locally advanced or recurrent head and neck cancer are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Head and Neck Neoplasms; Humans; Methotrexate; Peplomycin

This report concerns a 64-year-old male suffering from advanced hypopharyngeal cancer. This patient was treated with four courses of combination chemotherapy including VPCP (a combination of VCR, PEP, CDDP and PEP) regimen as neo-adjuvant chemotherapy. And radiotherapy was given as a secondary treatment; Linac. 60 Gy/6 weeks. He showed no tumor masses in the hypopharynx following this combination chemotherapy. No recurrence has been found under endoscopy for one year after the treatment with combination chemotherapy. It thus seems that neo-adjuvant chemotherapy prior to surgery and/or radiation including cisplatin, peplomycin and other agents is very useful as a multimodal treatment for cancer of the hypopharynx.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Humans; Hypopharyngeal Neoplasms; Male; Middle Aged; Peplomycin; Pharyngeal Neoplasms; Remission Induction; Vincristine

Chemotherapy with bronchial artery infusion (BAI) was given to 34 patients with primary lung cancer. Treatment regimens usually employed cis-diammine-dichloroplatinum (CDDP) plus peplomycin for squamous cell carcinoma, and CDDP plus vindesine for adenocarcinoma. The provisional therapeutic effects were evaluated roentgenographically with reference to histological type, T factor and degree of vascularization. Out of 10 cases of squamous cell carcinoma, 7 cases (70%) showed tumor regression greater than 50%, in contrast to 4 of 17 cases (23.5%) of adenocarcinoma. The effects in cases of squamous cell carcinoma were correlated with tumor vascularity. Twenty-two surgically treated cases were examined for the histological effects of BAI. Five of 6 cases (83.3%) of squamous cell carcinoma showed IIb effects by Shimosato's criteria. These results showed that the therapeutic effect of BAI was excellent in cases of squamous cell carcinoma in comparison with cases of adenocarcinoma. Serious side effects including esophago-bronchial fistula, massive hemoptysis and esophageal ulcer were observed in 4 cases.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vindesine

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Organoplatinum Compounds; Peplomycin

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchial Arteries; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Male; Middle Aged; Mitomycins; Peplomycin; Vincristine

We have been treating advanced cancer of the cervix uteri with intra-arterial cisplatin (CDDP) and peplomycin (PEP) (injected into the bilateral internal iliac artery), combined with radiotherapy and hysterectomy. Concomitant angiotensin II (ATII) administered by intravenous drip infusion was found to double tumoral blood flow and thereby to enhance the efficiency of the intra-arterial chemotherapeutic regimen. In the present study, hypertensive intra-arterial chemotherapy utilizing ATII was administered to a small group of patients with advanced cancer of the cervix uteri while ascertaining the increase in intratumoral blood flow by intra-arterial digital subtraction angiography. The subjects were 10 patients with stage IIb or more advanced cancer of the cervix uteri.. A 2-fold or greater increase in tumoral blood flow was attained in those patients who showed concurrently a 1.5 fold or greater increase in mean blood pressure and an increase in mean blood pressure to 150mmHg or higher. In 2 patients, ATII infusion failed to raise blood pressure to a therapeutically adequate level. At 1 week after the treatment in question histological evidence indicated unequivocal degenerative changes and necrotic changes in tumor cells. Many plasma cells, lymphocytes + and granulocytes appeared around necrosis changed carcinoma nests.

Topics: Adult; Aged; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Iliac Artery; Infusions, Intravenous; Injections, Intra-Arterial; Middle Aged; Peplomycin; Radiographic Image Enhancement; Regional Blood Flow; Subtraction Technique; Uterine Cervical Neoplasms

Urethral carcinoma in 2 females has been treated with irradiation together with adjunct chemotherapy. In case 1, a 73-year-old female with squamous cell carcinoma was successfully treated with irradiation of 4,000 rad and peplomycin of 60 mg intravenously given. She has been free from the disease for the past 43 months. In case 2, a 61-year-old female with transitional cell carcinoma was initially treated with irradiation of 5,000 rad together with peplomycin 90 mg, which was followed by another 5,000 rad irradiation. The tumor recurred and the patient was operated on for cystourethrectomy and partial resection of the vagina. A further chemotherapy of cisplatin, peplomycin, and mitomycin C was instituted. She died of the tumor recurrence 23 months after the first visit to our clinic. Diagnosis and treatment modalities on the female urethral carcinoma are briefly discussed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Mitomycin; Mitomycins; Peplomycin; Radiotherapy Dosage; Urethral Neoplasms

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchoalveolar Lavage Fluid; Bronchopneumonia; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Lung; Lung Neoplasms; Male; Methotrexate; Middle Aged; Peplomycin; Vincristine

Topics: Aged; Aged, 80 and over; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Peplomycin

A 40-year-old male with advanced penile cancer, whose left inguinal node was ulcerated at the time of initial presentation, underwent multimodal therapy. Four cycles of chemotherapy were given from September 20, 1984 to February 8, 1985. Partial penectomy and left ilioinguinal lymphadenectomy with removal of left groin ejaculation were performed on February 20, 1985, followed by right ilioinguinal lymphadenectomy on March 20, 1985. The skin defect of the left groin was covered with tensor fascia lata myocutaneous flap. The patient is alive with no evidence of disease 30 months after the surgery.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Fascia Lata; Humans; Male; Methotrexate; Muscles; Penile Neoplasms; Peplomycin; Skin Transplantation; Surgical Flaps; Thigh; Vincristine

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Peplomycin

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Head and Neck Neoplasms; Humans; Male; Methotrexate; Middle Aged; Peplomycin

Cases of maxillary cancer treated at our institute can be divided into two groups. In the first group (1971-1982, N = 85), we treated maxillary cancer by preoperative intraarterial infusion of 5-FU and Linac X-ray irradiation (60 Gy/6 weeks), followed by maxillectomy. In the second group (1982-1986, N = 32), we further combined intraarterial or intravenous chemotherapy using CDDP preoperatively or postoperatively depending upon the stage of the cancer. Five-year survival rate was 64.7% in the first group and 73.9% in the second. In the first group, the most frequent cause of death was distant metastasis without local recurrence. In the second group, the histopathological effect of chemotherapy and radiotherapy was improved with a reduced frequency of distant metastasis and it has now become possible to have 5-year survivors from among N2 and M1 cases. Judging from the histopathological effects of chemotherapy and radiotherapy, it seems possible to treat T2 and some T3 cases of maxillary cancer without performing maxillectomy. However, in T4 and most of T3 cases in which early recurrence is difficult to detect, it seems safer to combine total maxillectomy primarily.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Injections, Intra-Arterial; Lymphatic Metastasis; Male; Maxillary Neoplasms; Melanoma; Middle Aged; Peplomycin

Advanced squamous cell carcinoma of the head and neck, lung, esophagus, and uterine cervix is still a challenging cancer to the medical practice. We have treated 23 such patients with a combination of cis-platinum, vincristine, and peplomycin. Cis-platinum was given at a dose of 60 mg/m2 on day 1, and 1.0 mg/m2 of vincristine was given on day 3, followed 6 hours later by peplomycin 10 mg/day by continuous infusion iv or sc over the next 5 days. This combination was given every 3 weeks. The overall response rate was 71% for 17 evaluable patients, including one complete response. The median duration of response and survival was 2 and 5 months, respectively. Six other patients with esophageal and cervical carcinoma were treated with two cycles of this combination followed by radical radiation therapy or surgery. Five of them achieved significant response prior to radical treatment. Major side effects were nausea, vomiting, alopecia, and mild myelotoxicity, which were acceptable. This regimen, with a high response rate and acceptable toxicity, warrants further investigation.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Evaluation; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Peplomycin; Time Factors; Uterine Cervical Neoplasms; Vincristine

Topics: Administration, Intravaginal; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cervix Uteri; Cisplatin; Female; Humans; Infusions, Parenteral; Peplomycin; Tissue Distribution; Uterine Cervical Neoplasms

Based on the cell types in bronchogenic carcinoma, we treated 123 patients with different regimens of combination chemotherapy. The chemotherapy regimens consisted of CAP (cyclophosphamide + adriamycin + platinum) for 60 patients with adenocarcinoma and large cell carcinoma, PP (peplomycin + platinum) for 29 patients with squamous cell carcinoma and CAV (cyclophosphamide + adriamycin + vincristine) for 35 patients with small cell carcinoma. These regimens were repeated every 4 weeks for at least 2 cycles. The response rates for CAP, PP and CAV were 18.3% (11 PR), 20.7% (6 PR) and 60% (10 CR + 11 PR), respectively. Median survival time (MST) was 12.5 months for CAP, 8.5 months for PP and 9.5 months for CAV. Responders had a significantly (P less than 0.002) improved survival (MST, 15.5 months) compared to non-responders (MST, 7.5 months) in small cell carcinoma. However, there was no significant difference between responders and non-responders in CAP and PP. Survival of patients with PS 0-1 was significantly better than that with PS 2-3 in all treated patients. Nausea and vomiting were severe in patients treated with platinum-based polychemotherapy. There was no renal failure although a transient increase of serum creatinine was noted in CAP and PP. Myelosuppression was mild to moderate in all patients treated with CAP, PP and CAV.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin; Peptichemio; Vincristine

The effect of PPM therapy, consisting of cisplatin, peplomycin and mitomycin C, was evaluated in 15 cases of squamous cell lung cancer. Ten partial responses were achieved in primary cases and the response rate was 66.7%. Nephrotoxicity was well controlled with a continuous infused drip and FOM. The nausea and vomiting were reasonably well controlled with methylprednisolone and metoclopramide. Severe interstitial pneumonitis occurred in 5 cases (33.3%). PPM therapy is considered to be a very useful combination chemotherapy for squamous cell lung cancer but careful attention must be paid to pulmonary toxicity.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Infusions, Parenteral; Isotonic Solutions; Lung Neoplasms; Male; Methylprednisolone; Metoclopramide; Middle Aged; Mitomycin; Mitomycins; Nausea; Peplomycin; Ringer's Lactate

Squamous cell carcinoma with hypercalcemia and leukocytosis arising from burn scars in a 45-year-old man is reported. Hypercalcemia and leukocytosis improved with pepleomycin treatment and worsened with recurrence of the tumor. Serum levels of parathyroid hormone, prostaglandin E and 25-OH-Vitamin D were within normal limits. Autopsy did not disclose any bone metastases or abnormalities of the parathyroid glands. It is suggested that hypercalcemia and leukocytosis were due to factors produced by the squamous cell carcinoma. This is the fifth reported case of cutaneous squamous cell carcinoma associated with hypercalcemia in the absence of bone metastasis or parathyroid gland abnormalities.

Topics: Bleomycin; Burns; Carcinoma, Squamous Cell; Cicatrix; Humans; Hypercalcemia; Leukocytosis; Male; Middle Aged; Peplomycin; Skin Neoplasms

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Mouth Neoplasms; Peplomycin

Hyperthermo-chemo-radiotherapy (HCR) was prescribed for a patient with superficially spreading esophageal cancer, since severe lung dysfunction presented too great a surgical risk. Viable cancer cells completely disappeared after HCR and 8 months later, at this writing, the patient is living in good condition. Conservative treatment with HCR for patients with esophageal cancer is effective for carefully selected patients.

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Cobalt Radioisotopes; Combined Modality Therapy; Esophageal Neoplasms; Humans; Hyperthermia, Induced; Male; Peplomycin; Radioisotope Teletherapy

Twenty-three patients with squamous cell carcinoma were treated with a combination chemotherapy consisting of cisplatin, vincristine, and peplomycin. Overall response rate was over 70% including complete disappearance of tumors in one patient. Peplomycin was given by continuous i.v. or s.c. infusion using a micro-infusion pump. All the patients experienced some degree of nausea, vomiting, and hair loss. Phlebitis and induration of injection sites with subsequent local pigmentation were frequently encountered. Nausea and vomiting were caused mainly by cisplatin, but more than 60% of the patients experienced transient increase of anorexia or nausea in the period of peplomycin administration. Eruption with skin excoriation or pigmentation along scratch dermatitis were seen in 5 patients. These side effects were well tolerated, and high fever which is commonly observed in one-shot therapy did not develop in any patient. Pulmonary fibrosis was also not seen. Peplomycin should be given by low-dose continuous infusion because of its low toxicity and comparable antineoplastic activity to one-shot therapy.

Topics: Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Eruptions; Female; Humans; Infusions, Parenteral; Lymphoma; Male; Middle Aged; Peplomycin; Phlebitis; Vincristine

Multi-drug combination therapy with CDDP, 5-FU and PEP was performed in 23 patients with malignant tumors in the head and neck region, and 2 CR patients and 9 PR patients were obtained with a response rate of 47.8%. The present therapy (CFP therapy) is considered to be especially effective against patients at low performance status grades with poorly differentiated squamous cell carcinoma which is located in regions receiving an abundant blood supply like the oral cavity. It is advisable to perform more than 2 courses of treatment as an induction chemotherapy. With respect to the method of administration of PEP, further study will be made in the future.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Middle Aged; Peplomycin; Rhabdomyosarcoma

The relationship between morphological manifestations and cell kinetic changes of three lung cancer cell lines after exposure with chemotherapeutic agents was studied. After treatment with Cis-dichloro diammine platinum (II) (CDDP), an increase in cells of G2/M compartment at first, and then of S compartment was observed. As for the morphological manifestation, enlarged nuclear cells were more frequently observed. These cells seemed to be in S-G2/M compartment and to die finally. However a part of cells escaped from complete blockade may show multiple nuclei. Also after treatment with Etoposide (VP-16), an increase of G2/M compartment was observed, and on the morphological manifestation enlarged nuclear cells or double-or multiple-nuclear cells were observed. As these cells seemed to enter into G2/M compartment immediately. Cell destruction was thought to be started earlier compared with other two drugs. After treatment with Peplomycin (PEP), its effects on cell cycle traverse were only minimum accumulation of G2/M compartment in high PEP concentration. However concerning the morphological manifestation, many cells treated with PEP revealed enlarged, double or multiple nuclei. This suggests that morphological manifestation may reflect cytocydal effects more dominantly than cell cycle traverse. Each chemotherapeutic agent influenced the morphological manifestation and the cell kinetics of human lung cancer cells characteristically. It seemed to be important to study these relations in order to estimate the effect of chemotherapeutic agents and the therapeutic efficacy on cancer cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Cycle; Cell Line; Cisplatin; DNA, Neoplasm; Etoposide; Flow Cytometry; Humans; Lung Neoplasms; Peplomycin

Topics: Bleomycin; Carcinoma, Squamous Cell; Combined Modality Therapy; Humans; Mouth Neoplasms; Peplomycin; Preoperative Care; Radiotherapy Dosage

Ninety-three patients with head and neck cancer were treated with combined cisplatin-peplomycin chemotherapy (CP therapy). Cisplatin (CDDP) 50 mg/m2 i.v. (intravenous) or i.a. (intraarterial) over 2 hr was given with hydration and mannitol diuresis on day 1. From day 2 through day 6, peplomycin (PEP) 5 mg/day was administered by 5-hr i.v. or i.a. infusion, or 24-hr continuous hypodermic injection. Of 85 who were evaluable, there were 22 complete responses or CR (26%) and 36 partial responses or PR (42%), with an overall response rate of 68%. Concerning of the route of administration, i.a. infusion obtained the higher CR and overall response rates than i.v. infusion. Effectiveness was clearly greater in previously untreated cases than in cases that had received some previous therapeutic modality. Looking at response in relation to the number of the courses, at least 2 courses of CP therapy are required. Side effects were recognized in 68 out of 87 evaluable cases (78%). Nausea and vomiting were the most common (62%). Renal toxicity was observed in 24% and was mostly transient. From the above results, it is considered that the CP therapy is effective, not only for the palliative treatment of advanced and recurrent cancer of the head and neck, but also as neo-adjuvant chemotherapy of stage III and IV cases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Peplomycin

Neo-adjuvant chemotherapy, followed by definitive surgery and/or radiotherapy was utilized in nine patients with carcinoma of the hypopharynx and cervical esophagus starting in December, 1983. They were treated with combination chemotherapies which included CDDP, PEP (BLM), and MTX. The patients' ages ranged from 52 to 70 years with an average of 57. The histologic types were all squamous cell carcinoma and performance status was 1 in all cases. There were 7 stage III and 2 stage IV. Of 9 patients, 3 showed complete response and 6 showed partial response of the primary tumor with an overall response rate of 100%. Of 8 patients, 3 showed complete response and 2 showed partial response of the metastatic node with an overall response rate of 62.5%. Toxic effects included alopecia in 9 patients, nausea/vomiting in 7, eczema in 4, RBC below 350 X 10(4)/mm3 in 5, WBC below 3000/mm3 in 1, peak serum creatinine above 2 mg/dl in 1. All patients except one with renal toxicity were able to start definitive treatment soon after chemotherapy, the primary and regional lesions being subsequently well controlled in all 9 patients. Neo-adjuvant chemotherapy appears to be very effective for the reduction of tumor bulk. This multidisciplinary therapy should be expected to increase survival rate.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Hypopharyngeal Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Peplomycin; Pharyngeal Neoplasms

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Cisplatin; Drug Synergism; Head and Neck Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Peplomycin

In order to study the effect of Bestatin on superficial bladder cancer, the drug was used in combination with hyperthermia and Peplomycin therapy. The study was made using the following 2 groups. Group 1; Hyperthermic treatment with Peplomycin was used in 6 cases of bladder cancer. Group 2; Bestatin was given in combination with hyperthermia and Peplomycin in 15 cases of bladder cancer. As a result, complete or partial regression was obtained in 1 and 5 cases in Groups 1 and 2 respectively. Therefore, the combined use of Peplomycin and Bestatin in hyperthermic treatment for superficial bladder cancer appeared to be effective. Degeneration of tumor cells, irregularity of tumor structure, interstitial edema, fibrosis and cell infiltration were observed in the surgical specimens taken from effective cases, although the mechanism of action of Bestatin on tumors was clearly demonstrated upon histological examination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Hyperthermia, Induced; Leucine; Male; Middle Aged; Peplomycin; Urinary Bladder Neoplasms

A new multidisciplinary treatment for head and neck cancer was shown by focusing on the maxillary and oropharyngeal carcinoma. Neo-adjuvant chemotherapy which consists of cisplatin and peplomycin was incorporated into it. In terms of maxillary carcinoma, 2 courses of chemotherapy were given with an interval of 2 weeks, followed by radiotherapy (40 Gy) combined with intraarterial chemotherapy (5-FU). When no cancer cells were detected at the completion of this therapy, adjuvant chemoimmunotherapy was given. When an apparent tumor was still revealed by CT, radical surgery was performed. When cancer cells were detected only by histological examination, additional radiotherapy up to 60 Gy was given by Linac. The results obtained were analysed in 14 cases. We also presented another type of multidisciplinary treatment in oropharyngeal carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Male; Maxillary Neoplasms; Oropharyngeal Neoplasms; Peplomycin; Pharyngeal Neoplasms; Radiotherapy Dosage

Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), established using human bladder cancer xenografts in nude mice were applied for advanced urothelial cancer. VPM-CisCF (I) consisted of 0.4 mg/m2 VCR on days 1 and 4, 2 mg/m2 PEP on days 1-7, 2 mg/m2 MTX on days 2, 3, 5 and 6, 20 mg/m2 CDDP on days 8, 20 mg/m2 Ara-C on days 8 and 13, and 150 mg/m2 5-FU on days 10-12. VPM-CisCF (II) consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PEP on days 1-4, 3 mg/m2 MTX on days 2 and 3, 35 mg/m2 CDDP on day 4, 20 mg/m2 Ara-C on days 4 and 7, and 200 mg/m2 5-FU on days 5 and 6. These doses were adjusted for each case: the above mentioned dose x [(80/(40 + Age))2 + (Karnofsky's performance status/100)2]. VPM-CisCF (I) was administered to 6 patients (bladder cancer and transitional cell carcinoma), intra-arterially in two cases. One patient showed a complete response and survived for 7 months, three partial response (PR) surviving for 13, 8 and 37 (arterial-infused case) months, one showed minor response (MR) surviving for 4 months, and one had no change (NC) surviving for 5 months. VPM-CisCF (II) was administered to 11 patients (1 ureteral cancer, 1 renal pelvic cancer, 9 bladder cancer, and 10 transitional cell carcinoma except a case of mixed type of transitional cell carcinoma and squamous cell carcinoma). Four of the patients who had PR survived for 9, 8, 8 and 7 (alive) months, two who had MR survived for 8 and 4 months, three who had NC survived for 6, 4 and 4 months, and who two had progressive disease survived for 8 and 6 months. The major toxicities were myelosuppression and gastrointestinal symptoms, especially nausea and vomiting, but the treatment was well-tolerated.

Topics: Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Cytarabine; Female; Fluorouracil; Humans; Kidney Neoplasms; Male; Methotrexate; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Peplomycin; Ureteral Neoplasms; Urinary Bladder Neoplasms; Vincristine

Eight patients with gynecologic cancer (cervix: 6, corpus: 1 and vulva: 1) were treated with combination chemotherapy, PPM therapy consisting of continuously infused PEP 4mg/m2 days 1-5, CDDP 13 mg/m2 days 1-5, and MMC 3mg/m2 day 1. This was repeated every three to five weeks. Six of the eight patients were evaluable, two had a complete response and one had a partial response, for an overall response rate of 50%. Because of hematological toxicity, blood transfusion was carried out in four patients. Nephrotoxicity and pulmonary toxicity were slight. Nausea and vomiting were controlled with dexamethasone and domperidone. PPM therapy is considered to be an effective and useful combination chemotherapy for patients with gynecologic cancer.

Topics: Adenocarcinoma; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Uterine Cervical Neoplasms; Uterine Neoplasms; Vulvar Neoplasms

Pepleomycin is a derivative of bleomycin, which is less toxic to the host but possesses greater antitumor activity. Experiments are described here in which Chinese hamster V-79 cells in culture and a murine squamous cell carcinoma in vivo have been used to obtain survival curves for pepleomycin alone or in combination with radiation. In both systems the survival curves for pepleomycin alone are biphasic, and this drug proved to be twice as effective as bleomycin. Further, in contrast to bleomycin, which showed simple additivity with radiation, pepleomycin potentiated radiation injury to the tumor cells both in vivo and in vitro. Therefore, pepleomycin may be superior to bleomycin not only in drug therapy but also in combined modality therapy.

Topics: Animals; Bleomycin; Carcinoma, Squamous Cell; Cell Line; Cell Survival; Combined Modality Therapy; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Female; Kinetics; Male; Mice; Peplomycin; Time Factors

Topics: Adenocarcinoma; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Genital Neoplasms, Female; Humans; Melanoma; Peplomycin; Tumor Stem Cell Assay

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Male; Peplomycin; Pulmonary Fibrosis

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Peplomycin

Advances in the treatment of inoperable non-small cell lung cancer (NSCLC) have been falling behind the recent results obtained for small cell lung cancer (SCLC) which had been considered the more malignant type with the shortest survival time. Recently, however, with the introduction of cisplatin, the results of combination chemotherapy for NSCLC have shown a degree of advancement so that an average response rate of 40% and a median survival time (MST) of 8-10 months can be obtained. Our method of combination chemotherapy, PPM (cisplatin, peplomycin, mitomycin C), resulted in an overall response rate of 44% (40% squamous, 29% adeno, 64% large) and an MST of more than 23.3 months in responders. With PFM (cisplatin, 5FU, mitomycin C), response rate was 35% and an MST of 18.7 months was obtained for adenocarcinoma responders. It can therefore be said that we have achieved a new degree of success in the treatment in NSCLC.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Lung Neoplasms; Mitomycin; Mitomycins; Peplomycin

Combination chemotherapy of cisplatin (CDDP) with bleomycin (BLM) or peplomycin (PEP) has exhibited clinical efficacy against squamous cell carcinomas. The combination of CDDP with PEP was studied using five human squamous cell carcinomas in nude mice. When CDDP was administered before PEP treatment, the combination effect was more pronounced than when CDDP was administered after PEP treatment. Especially, when CDDP was administered 5 or 3 days before PEP treatment, marked delay in growth was shown in 4 out of the 5 human carcinomas. From these results, it is thought that human heterotransplanted tumors in nude mice may provide important information in studies of combination chemotherapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cell Division; Cisplatin; Drug Synergism; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Peplomycin

Effects of BAI therapy on 86 cases of lung cancer were evaluated in three groups: single-use of MMC group after intravenous PEP administration (PEP (iv).MMC group), PEP and MMC combination use group (PEP + MMC group) and single use of MMC group. Tumor regression rate determined by chest X-ray film 2 or 3 weeks after BAI was highest in the PEP (iv).MMC group followed by the PEP + MMC and MMC group. Cavity formation was more typical in the group treated with PEP + MMC. Histopathological effects were best for the PEP + MMC group followed by those of the PEP (iv).MMC and MMC group. As for side effects, pulmonary fibrosis and necrotizing bronchitis were noted in 8% of the PEP + MMC group, but side effects in the other two groups were mild. In conclusion single use of MMC after intravenous PEP administration was found to be the best way to give BAI in these three groups.

Topics: Adenocarcinoma; Bleomycin; Bronchial Arteries; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Mitomycin; Mitomycins; Peplomycin

Preoperative arterial infusion of peplomycin was carried out on 15 cases of Stage I or II cancer of the cervix, and the value of arterial infusion chemotherapy with peplomycin and its efficacy as a preoperative therapy in cervical cancer were evaluated by analysis of (1) histological changes, (2) localization of the drug in tissue, and (3) tissue concentration of the drug in the completely resected tissues, with the following results: The chief histological change was a regression of cancer nests accompanied by degeneration and necrosis of cancer cells. This change was clearer at the head of infiltrating cancers than at their superficial layer or center. Peplomycin was localized with high activity at the disintegrated part of cancer nests, i.e., its activity was closely correlated to the severity of histological change. Time-course changes in its localization suggested the vessel wall----stroma----cancer as the route of its transport. The tissue concentration of peplomycin was maintained high over a long time. Particularly in the portio vaginalis, the time course decline of the concentration was gentle. From the above findings, arterial infusion of peplomycin was considered to be an effective method of chemotherapy for cervical cancer, and worth being tried as a preoperative therapy too.

Topics: Adult; Bleomycin; Carcinoma, Squamous Cell; Female; Humans; Infusions, Intra-Arterial; Middle Aged; Peplomycin; Uterine Cervical Neoplasms

Twelve patients with unresectable and recurrent non-small cell carcinoma of the lung were treated with a combination chemotherapy consisting of cis-platinum and adriamycin. The overall response rate was 42% with two complete responses and three partial responses. The durations of response were 9+ and 8.5+ months in two complete responses, and 7.5+, 5.5+ and 2.5 months in three partial responses. The overall median survival was 8 months ranging 3.5+ to 16+ months. Three patients had leukopenia less than 2,000/mm3, two patients had thrombocytopenia less than 100 X 10(3)/mm3, and four patients had hemoglobin decrease of 3 g/dl or more. Severe nausea occurred in nine patients, whereas vomiting did in seven patients. Nearly total alopecia was observed in all patients. Renal toxicity in four patients was also observed, but was reversible. We believe that the combination chemotherapy with cis-platinum and adriamycin is promising in the management of patients with non-small cell carcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin

Six patients with recurrent carcinoma of the uterine cervix were treated with a combination of peplomycin, adriamycin and cis-platinum (PAP). The PAP regimen consisted of peplomycin at a dose of 5 mg/day, continuous i.v. drip on days 1-7, adriamycin at a dose of 40 mg/m2 i.v. on day 1, and cis-platinum at a dose of 40 mg/m2, continuous i.v. drip on day 1, repeating at five to six week intervals. Three complete responses and three partial responses were obtained in six evaluable patients. Toxicities included mild to moderate nausea and vomiting, alopecia, nephrotoxicity, and myelosuppression, were generally manageable. We have concluded that PAP regimen is one of the useful regimens for recurrent uterine cervical carcinoma with pulmonary metastasis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Uterine Cervical Neoplasms

The serum carcinoembryonic antigens (CEA) levels in 177 advanced lung cancer patients were studied to assess their value for the prognosis and indicating the effectiveness of chemotherapy. The relationship of pretreatment CEA levels with histology and stage of disease was also examined. Levels in excess of 5 ng/ml and 20 ng/ml were found in 55% and 32% of lung cancer patients, respectively. The elevated CEA levels were more frequently observed in patients with adenocarcinoma (65% in excess of 5 ng/ml) and extensive disease, but pretreatment CEA levels were not significantly correlated with the histology and clinical stage of disease. In 102 patients with adenocarcinoma, there was no significant difference of survival time in each patient with CEA levels less than 5 ng/ml, 5.0 less than or equal to - less than 20 ng/ml and in excess of 20 ng/ml; median survival time was 7, 7, 8 mo, respectively, and response to chemotherapy was not significant in each of these groups. Serial serum CEA measurements in patients with pretreatment levels in excess of 20 ng/ml correlated well with changes in disease status reflecting clinical response to chemotherapy. Mean percent changes of CEA levels to pretreatment levels were-77.4% in patients with partial response (PR), -55.6% in those with minor response (MR), -4.0% in patients with no change (NC) and +79.0% in patients showing progressive disease (PD). There was a significant difference in the percent changes of CEA levels between patients with an objective response (PR) and patients who had none (MR + NC) (p less than 0.02). CEA levels of all patients who had PD increased or unchanged. Serial measurements of serum CEA are useful in patients whose pretreatment levels are more than 20 ng/ml for monitoring the response to chemotherapy, and may be a useful noninvasive technique for patients with unmeasurable disease as a monitor of tumor burden in response to chemotherapy and recurrent disease.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carbazilquinone; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Humans; Lung Neoplasms; Mitomycin; Mitomycins; Nimustine; Nitrosourea Compounds; Peplomycin; Vinblastine; Vincristine; Vindesine

In the period between November 1972 and December 1982, 27 patients with nasopharyngeal carcinoma were treated. The male to female ratio was 20:7. and ages ranged from 17 to 71 years with a median of 46. Most of the cases were classified as stage 4. Histological findings according to the WHO classification revealed undifferentiated carcinoma in two-thirds of all cases. The cumulative survival rate was 41.9% over a three-year-period and 17.1% over a five-year-period. Both primacy lesion and regional lymph node metastases were well controlled by radiation therapy. In patients with cranial nerve palsy and/or destruction of the skull base, distant metastasis developed severely later. Most of the distant metastases were found in bone and/or in the lung. In 14 of the 27 cases, systemic chemotherapy using various drugs, either alone or in combination, was performed. No complete response was obtained. Partial response was observed when adriamycin and vincristine were used in combination. Minor response was observed when pepleomycin or adriamycin was used alone. The sequential combination of bleomycin and mitomycin-c also produced minor response. Pre-radiation chemotherapy is recommended to obtain more effective results. The combined use of cis-diamminedichloroplatinum (cisplatin) and pepleomycin (peplomycin) was reported to be effective in nasopharyngeal carcinoma. The testing of pre-radiation chemotherapy using this combination is encouraged for in the treatment of nasopharyngeal carcinoma.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Nasopharyngeal Neoplasms; Peplomycin

Two cases of fatal pneumonitis induced by pepleomycin, a new antitumour antibiotic analogous to bleomycin, are described. In the first case, the patient received radiation in combination with intra-arterial administration of pepleomycin to a total dose of 100 mg. for the treatment of an epidermoid carcinoma of the maxilla. The pulmonary changes were noted two weeks after cessation of the chemotherapy and the patient died of pulmonary insufficiency despite intensive therapy with antibiotics and a steroid. The other case with an epidermoid carcinoma of the cheek and oropharynx was treated by radiation and pepleomycin given to a total dose of 205 mg. Pepleomycin was replaced by predonin soon after bilateral shadows were noticed on a chest radiograph, but the patient died of pneumonitis 10 months later. Various factors which may affect the development of pulmonary toxicity by pepleomycin are discussed.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Female; Humans; Male; Maxillary Neoplasms; Middle Aged; Mouth Neoplasms; Peplomycin; Pharyngeal Neoplasms; Pneumonia

Pneumonitis-fibrosis which was induced by the treatment with antineoplastic agent(s) and/or irradiation was encountered in 37 (14.1%) of a total of 515 patients with lung cancer who had been treated in our institute during a period of seven years from 1976 through 1982. Of 251 patients who had been treated with bleomycin or pepleomycin alone or in combination with other antineoplastic agent(s) or irradiation, 46 (18.3%) had pneumonitis-fibrosis and 19 (7.6%) died therefrom. It was revealed that the patients over 50 years of age, whose PaO2 and % VC prior to the treatment with bleomycin were less than 79 mmHg and 79% respectively appeared to be predisposed to bleomycin pulmonary toxicity. Most of the pneumonitis which developed in these patients was progressive and fatal. Daily oral administration of 10 mg of prednisolone was in effective for the prevention of bleomycin-induced pneumonitis-fibrosis. A sudden decrease of PaO2 and a sharp elevation at a certain point in time during treatment were indicative of the fatal outcome of toxic pulmonary complications. Thoracic irradiation prior to, concomitant with or after bleomycin therapy enhanced the pulmonary toxicity of bleomycin. Therefore, combination therapy should be avoided. A continuous intravenous infusion may be the most effective and least toxic method to administer bleomycin.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Peplomycin; Prognosis; Pulmonary Fibrosis

The effect and toxicities of Cis-containing combination chemotherapy were tested in 28 patients with primary lung cancer. All patients were treated with 80 mg/m2 Cisplatinum on the first day and 750 mg ftorafur p.o. every day. In addition to these drugs, patients with squamous cell cancer were treated with continuous subcutaneous infusion of 4 mg/m2 Peplomycin for 5 days and one shot i.v. of 4 mg MMC. Patients with adeno- and large cell cancer were treated with 30 mg/m2 Adriamycin and 4 mg MMC, while patients with small cell cancer were given 150 mg/m2 VP-16 p.o. for 5 days. The following results were obtained. Of 22 evaluable patients, overall response rate was 50%. In each histologic type, response rate was 50% (5/10) for squamous cell carcinoma 50% (4/8) for adenocarcinoma 33% (1/3) for large cell carcinoma and 100% (1/1) for small cell carcinoma. No CR was obtained in this series. Main side effects due to Cisplatinum were nausea, vomiting, loss of appetite, mild leukopenia and thrombocytopenia, mild elevation of serum creatinine and BUN and alopecia, all of which were transient. Interstitial pneumonitis was observed in 40% of patients with squamous cell cancer. Two patients with adenocarcinoma died within 3 weeks after treatment due to embolism of the abdominal aorta and myocardial infarction probably caused by treatment with Adriamycin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Tegafur

Twenty patients with unresectable non-small cell lung cancer were treated with a combination chemotherapy of cisplatin (30 mg/body i.v., days 1-5), peplomycin (5 or 8 mg/body continuous infusion, days 1-5), mitomycin C (4 mg/body i.v., day 1), and vincristine (2 mg/body i.v., day 1), of 15 patients evaluable for response (9 with squamous cell carcinoma, 2 with adenocarcinoma, nd 4 with large cell carcinoma), the overall response rate was 46.7% with 7 partial responses. The median survival period for responders. Toxicity included hair loss, nausea and/or vomiting, mild to moderate myelosuppression, nephrotoxicity, and pulmonary toxicity, all of which was manageable. This four-drug combination chemotherapy is concluded to be effective for non-small cell lung cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vincristine

A phase II trial has been performed in squamous cell carcinoma of the lung using peplomycin. This compound is a bleomycin analogue with less pulmonary toxicity and a broader antitumor effect than bleomycin in experimental animal systems. Twenty-one evaluable patients were treated using a dose schedule of 5 mg/m2 twice weekly intravenously. None of the patients had previously received radiation or chemotherapy. The median dose of peplomycin received was 160 mg (range 45-254). One patient obtained a partial remission lasting 3 months. One out of 21 patients developed clinical symptoms and a decrease in the lung function test performed during treatment indicative of toxicity. Other manifestations of toxicity are comparable to those of bleomycin.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Drug Evaluation; Humans; Lung Neoplasms; Middle Aged; Peplomycin

Topics: Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Kinetics; Maxillary Neoplasms; Peplomycin; Tongue Neoplasms

A combination immunochemotherapy regimen containing cisplatin (20 mg, days 1-5), peplomycin (20 mg, days 2, 9, 16), +/- vinblastine (5 mg, days 1, 2), and picibanil (3-5 KE/week) was performed in twelve patients with advanced or recurrent uterine and ovarian cancers under intravenous hyperalimentation (IVH), except one patient receiving peplomycin by a continuous infusion method using IVH bag (10 mg/day for 5 days). This regimen was repeated every three weeks. Five (71.4%) of seven evaluable patients showed partial response. No patients yielded the complete disappearance of disease. No severe and lethal pulmonary or renal dysfunction occurred and all was well tolerated. In a regimen without vinblastine, myelosuppression, especially thrombocytopenia, occurred later compared to the regimen including vinblastine.

Topics: Adenocarcinoma; Aged; Biological Products; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Therapy, Combination; Female; Humans; Immunotherapy; Middle Aged; Ovarian Neoplasms; Peplomycin; Picibanil; Uterine Cervical Neoplasms; Uterine Neoplasms; Vinblastine

Eight esophageal squamous cell cancer patients were treated with local hyperthermochemotherapy plus ethanol in addition to bypass surgery and supraclavicular esophagostomy. Local hyperthermochemotherapy plus ethanol treatment was as follows: The esophagus was perfused for one hour using esophagostomy with warmed saline (42-44 degrees C) containing 6-10% ethanol, the overflowing saline was aspirated. Simultaneously, 15 mg Bleomycin or 10 mg Peplomycin was administered intravenously and 5 mg Bleomycin or Peplomycin was administered directly to the esophageal site. This procedure was repeated twice a week for a total of 10 to 24 times. Six of the 8 patients (75%) thus treated showed a shortening of the duration of the shadow defect in X-radiograms. In one case, the lesion was removed and the patient is doing well 9 months after the operation.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagoplasty; Ethanol; Female; Hot Temperature; Humans; Male; Methods; Middle Aged; Peplomycin

A neo-adjuvant chemotherapy as a preoperative and preradiation chemotherapy was studied in 60 cases of the head and neck cancers. Out of 60, 29 cases were treated with peplomycin (PEP) and 31 with combination chemotherapies which include vincristine (VCR), methotrexate (MTX), bleomycin (BLM), mitomycin C (MMC); VCR, MTX, BLM (Mathé); VCR, MTX, BLM, 5-FU, hydrocortisone (Price-Hill A); hydoxyurea, adriamycin, BLM; VCR, MTX, PEP; cisplatin (CPDD), PEP. In the group treated with PEP, CR was achieved in one case and PR in 14 cases with a response rate of 52%. Five-year survival by Kaplan-Meier's method after all treatment was 34%. In the group treated with combination chemotherapy, CR was achieved in 5 cases and PR in 19 cases with a response rate of 77%. Three-year survival of this group was 82%. Responders to PEP as well as combination chemotherapy were more often rendered disease-free after all treatment than non-responders. We concluded that two courses of VMP therapy (VCR, MTX, PEP) would be appropriate for the outpatients with advanced stage I or stage II, meanwhile two courses of CP therapy (CPDD, PEP) was inpatients with stage III or stage IV as a neo-adjuvant chemotherapy.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Male; Methotrexate; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vincristine

Topics: Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Female; Humans; Middle Aged; Peplomycin; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin

Eighteen previously untreated patients with squamous cell carcinoma of the lung were treated with a combination of a new bleomycin derivative, peplomycin and esquinon (PQ). One patient achieved a complete response (5.5%) and 5 patients a partial response (27.8%). Overall response rate was 33.3%. Median survival time of 6 patients with complete and partial response was 54 weeks and that of 12 patients with no change and progressive disease was 15 weeks. Toxicities included nausea and/or vomiting in 89%, fever in 61%, interstitial pneumonitis in 28% and leukopenia in 17%. PQ regimen appears to be effective in the treatment of squamous cell carcinoma of the lung.

Topics: Aged; Antibiotics, Antineoplastic; Azirines; Bleomycin; Carbazilquinone; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin

(1) Therapeutic effects of bronchial artery infusion (BAI) of peplomycin (PEP), a derivative of bleomycin, were examined in the 13 patients with lung cancer. The effectiveness of PEP was compared with that of 59 patients treated with mitomycin (MMC) or carboquon (CQ). (2) In all cases treated with PEP, histopathological effects revealed to be more than grade IIa of Shimosato's criteria, which were more effective than that with MMC or CQ. (3) Histopathological changes of the metastatic lymph nodes were similar to that of the main tumor. (4) In the cases treated with PEP, tumor decreased rates shown in the chest X-ray films 2 weeks after BAI were lower than that with MMC or CQ. Cavity formation in the tumor was recognized in 62% of the cases treated with PEP. (5) Low fever lasting several days after administration of BAI and GI symptoms such as nausea and vomiting were main side effects, which were mild and not so serious.

Topics: Adenocarcinoma; Azirines; Bleomycin; Bronchial Arteries; Carbazilquinone; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Mitomycins; Peplomycin

From experimental observations, Peplomycin was expected to be more active against a variety of tumors and to be less toxic for the lung than the parent compound. An intermittent dose(10mg. twice a week) of peplomycin was tested in patients with malignant lymphoma or squamous cell carcinoma who had failed conventional treatment. There were two cases of CR and five cases of PR in twelve cases with malignant lymphoma, and two cases of PR in fourteen cases with squamous cell carcinoma. Out of 26 cases treated with peplomycin, fever was seen in ten cases(38.5%) and pulmonary complication was seen in five cases (19.2%). These data obtained from peplomycin treatment were compared with the results obtained from our previous experiences with bleomycin. Response rate, spectrum and frequency of side reactions of peplomycin treatment were substantially identical with those of bleomycin treatment. However, remission duration and life span were much longer in peplomycin treatment. In this respect, peplomycin seems to be superior than bleomycin to a certain extent.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Female; Humans; Lymphoma; Male; Middle Aged; Peplomycin

A preliminary use of Peplomycin (PEP) was investigated in 14 patients with advanced esophageal cancer. PEP was given intermittently with a dose of 10 mg intravenously twice a week. As side effects there were observed fever elevation in 8 cases, stomatitis in 4 cases, erosion of the skin of the scrotum in 1 case and pigmentation in 1 case, respectively. Dyspnea associated with decrease of PaO2 was observed in 4 cases, which recovered promptly after discontinuing of the administration. Out of 10 evaluable cases, partial response was observed in 1, minor response in 1, no change in 3 and progressive disease in 5 cases, respectively. While the effect was only limited in these experiences, the local injection of PEP into or around the tumor using the external fistula of the remaining esophagus which was made at the time of by-pass operation was discussed.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin

A combined therapy of pepleomycin (NK-613) and radiation was performed in 15 cases of esophageal and cancer. Twelve cases out of 15 were inoperable, and 3 cases were operable. NK-631 was administered by drip intravenous injection at a dose of 5 mg per day for 3 consecutive days weekly, aiming at total dose of 60-120 mg. Tumor regression rates, which were measured by planimeter on esophagogram, were 42-92% (mean 72%): two cases were more than 90%, and more than 50% in 12 cases. An average of the survival period of 15 cases was 57 weeks with 7 cases (46.7%) of 1 year survival, 2 cases (13.3%) of 2 year survival. The side effects of NK-631 observed in the present study consisted of fever 6, stomatitis 2, skin rash 2, and reversible pneumonitis 2. This study suggests that NK-631 exhibit remarkable anti-tumor effects on esophageal carcinoma, and seem to be less toxic.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Radiotherapy Dosage

1. The therapeutic effects of pepleomycin seem superior to those achieved with bleomycin against squamous cell carcinoma and malignant lymphoma. 2. In basal cell epithelioma, carcinoma in situ (e.g., actinic keratosis, Bowen's disease), adenocarcinoma (e.g., mammary and genital Paget's disease), and adult soft tissue sarcoma, pepleomycin as well as bleomycin was clinically ineffective. 3. Of the two cases of stage IV malignant melanoma, pepleomycin combined with MeCCNU and VCR exerted a moderate effect against multiple disseminated skin metastases in one, and a slight effect against a VI rib metastasis in the other. 4. The sorts of side effects of pepleomycin were almost the same as those of bleomycin. Lung toxicities were less frequent under pepleomycin treatment than those under bleomycin treatment.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Drug Evaluation; Female; Humans; Japan; Lymphoma; Male; Melanoma; Middle Aged; Peplomycin; Skin Neoplasms

Topics: Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Delayed-Action Preparations; Female; Mice; Neoplasms, Experimental; Oils; Peplomycin; Skin Neoplasms

Topics: Adenocarcinoma; Aged; Animals; Bleomycin; Carcinoma, Squamous Cell; Cells, Cultured; Dogs; Drug Evaluation, Preclinical; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Rats

Topics: Aged; Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Cells, Cultured; Dogs; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Rats

Topics: Adenocarcinoma; Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Peplomycin