peplomycin and Mouth-Neoplasms

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

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

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

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

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

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

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

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

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

The pathogenesis of pulmonary fibrosis (PF) induced by bleomycin and its derivative, peplomycin (PEP), is insufficiently understood. To prevent PF and to administer PEP safely, we examined the influence of PEP on pulmonary function in 135 patients who underwent concomitant chemo (PEP + 5-FU)-radio (60Co) therapy and pulmonary function tests. In the inductive therapy, 5 mg of PEP was intramuscularly injected three times a week and a total of 41.6 +/- 14.3 mg was administered. Of the patients, 98 received oral azelastine hydrochloride (AZH, 4 mg/day) during the inductive therapy with the aim of prophylaxis of PF. The oxygen partial pressure in arterial blood (PaO2) only slightly decreased from 84.2 +/- 12.1 mmHg before treatment to 82.8 +/- 12.5 mmHg after treatment, while, carbon oxide diffusion (%DLco) decreased after treatment in most patients (p < 0.001, by paired t test) with mean values before treatment of 106.3 +/- 24.5% and after treatment 99.5 +/- 24.9%. The decrease of %DLco was associated with the dose of PEP until about 40 mg but further decreases of %DLco were not prominent. In the patients who underwent oral AZH, the decrease of %DLco weaker than that in patients without AZH: the decrease rates of %DLco in the former and latter were 4.3 +/- 9.4% and 14.1 +/- 15.9%, respectively. From the chest X-ray examination, mild PF was suspected in three patients but no advancement of PF or clinical symptoms were observed. From these results, it was concluded first that %DLco is more useful than PaO2 as the predisposing risk factor for PF, second that the decrease of %DLco depends on the dose of PEP until about 40 mg, third that AZH is expected to inhibit PEP-induced PF, and fourth that a small dose (20-40 mg) of PEP can be administered without inducing PF if care is exercised as to the patient's age, general condition and the value of %DLco in the use of PEP.

Topics: Aged; Antibiotics, Antineoplastic; Humans; Lung; Middle Aged; Mouth Neoplasms; Oxygen; Partial Pressure; Peplomycin; Pulmonary Fibrosis; Respiratory Function Tests

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

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 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

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

A 60-year-old woman was admitted to our hospital with a complaint of rough feeling on the oral mucosa and diagnosed as verrucous carcinoma with histopathological examination. She was treated with CPE chemotherapy, and showed a good response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia and anorexia. However, these were slight side effects. The patient is currently healthy with no recurrence after two years and 3 months. CPE chemotherapy is considered to be effective for a patient with verrucous carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Papillary; Cisplatin; Drug Administration Schedule; Etoposide; Female; Humans; Middle Aged; Mouth Neoplasms; Peplomycin; Remission Induction

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

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

Speech intelligibility has been investigated in 40 patients who had received a glossotomy because of tongue and/or mouth floor carcinomas after preoperative induction therapy. The results are summarized below. 1. Speech was clearer and better understood in intelligibility tests than by tests of single sounds. 2. Speech intelligibility was impaired in 12 patients. The impairment degree was mild (slight difficulty in understanding the spoken content) in 9 cases, where as the speech in the remaining patients was moderately or severely impaired. 3. Hardly any speech impairment resulted when the tongue resection was limited to the ipsilateral 1/3 of the tongue, where as the impairment was greater in cases who received a glossotomy over that limit. 4. Tongue mobility was related to speech intelligibility, and conservation of the tongue tip appeared important. 5. Aggressive induction therapy made limited surgical extirpation possible, and many patients speech functions were well preserved by conservative surgery. Together with good local control, aggressive induction therapy seemed to be beneficial for tongue and mouth-floor carcinomas.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Female; Fluorouracil; Humans; Male; Middle Aged; Mouth Neoplasms; Peplomycin; Preoperative Care; Radiotherapy Dosage; Speech Intelligibility; Tongue; Tongue 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

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

The goal in treating intraoral cancer is to obtain tumor control with preservation of shape and function of oral cavity. For T1, T2 lesions of the tongue, the floor of the mouth and the cheek mucosa, interstitial radiation therapy provides a control rate of 80-90% with excellent preservation of function. With surgical salvage for persistent or recurrent tumor, the ultimate control rate is 90-95%. Unfortunately, for more advanced lesions surgery is frequently required to obtain local control. The use of bleomycin or peplomycin in simultaneous combination with external radiation therapy provides a good chance of local control without surgery. For T1, T2 lesions of the lower gum and the cheek mucosa complete response rate is approximately 65% and 70% of these are cured without surgery. With surgical salvage for persistent or recurrent tumor the ultimate control rate is 90%. For most of the poor responders surgery or interstitial irradiation is required to control the tumor.

Topics: Bleomycin; Brachytherapy; Combined Modality Therapy; Humans; Mouth Neoplasms; Peplomycin; Prognosis

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

Fifty-three patients with postoperative recurrent epidermoid carcinomas of the head and neck were treated with BEAM, DP, MBD and CAP regimens. Complete response (CR) and partial response (PR) were achieved in 9% and 23% of all evaluable patients, respectively. Especially, in patients with oral cancer (17 cases), the response rate was only 23% (CR 0%, PR 23%). From our results, it was concluded that chemotherapy in any form must be palliative for a patient who has received prior unsuccessful radiotherapy or surgery. For previously untreated patients who present with Stage III or IV advanced carcinoma, combination chemotherapy with CDDP, MTX and PEP should be considered as the initial method of treatment. Adjuvant chemotherapy and intra-arterial chemotherapy for oral cancer should also be considered. Adjuvant chemotherapy combined with UFT and MTX is indicted to be effective for the prevention of local recurrence and micrometastases, but a further randomized study is necessary to confirm these findings.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Administration Schedule; Female; Humans; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Peplomycin; Tongue 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

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

The authors have studied preoperative chemotherapy for head and neck cancer since 1963, focusing on intra-arterial chemotherapy. The results obtained revealed that preoperative chemotherapy played an important role in the improvement of 5-year survival in maxillary sinus carcinoma and tongue carcinoma. However, functional and cosmetic damage after radical surgery has newly energed as problems to be resolved. The appearance of cisplatin has raised an important the level of effectiveness of cancer chemotherapy in recent years. Since the combination of cisplatin and bleomycin analogs revealed a remarkable synergistic effect in experimental chemotherapy, it has been used clinically as preoperative or preradiation chemotherapy for advanced Stage III and IV head and neck cancer. Under the above-mentioned circumstances, treatment for head and neck cancer has undergone various changes over the past twenty years. At present it is no exaggeration to say that the period in which dependence was placed on only surgery and/or radiation is over. The authors would like to emphasize that preoperative chemotherapy should be carried out as a part of multidisciplinary approach under a new concept of neo-adjuvant chemotherapy which includes not only preoperative chemotherapy but also preradiation chemotherapy. The role of preoperative chemotherapy, its current status and future prospects are discussed in this paper, looking back on the history of chemotherapy for head and neck cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Fluorouracil; Head and Neck Neoplasms; Humans; Infusions, Intra-Arterial; Maxillary Neoplasms; Mouth Neoplasms; Peplomycin; Pharyngeal Neoplasms; Preoperative Care; Tegafur; Uracil

Topics: Animals; Bleomycin; Cricetinae; Etretinate; Injections, Intraperitoneal; Mouth Neoplasms; Neoplasms, Experimental; 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