peplomycin and Uterine-Cervical-Neoplasms

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

The cervical cancer has already attained high survival rate and there is a little room to improve the prognosis. The examination of recurred patients reveals that the recurrence was often found in the cervix, parametrium, pelvic wall, and distant organs. More intensive treatment to such part may be of beneficial to reduce recurrence. Post operative radiation to the pelvis for high risk patients seemed to improve the survival rate, although some authors failed to show its merit. Radiation to the para-aortic lymph node is matter of controversial. Chemotherapy is now expected to play an important role to control or prevent distant metastasis. Considering these facts, improvement of prognosis of the cervical cancer will be expected by 1. early detection by mass screening and 2. centralization the treatment facilities in order to do the individualized and multidisciplinary treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Female; Humans; Lymphatic Irradiation; Mitomycin; Mitomycins; Peplomycin; Prognosis; Uterine Cervical Neoplasms; Vincristine

The objective of this study was to evaluate the response rate and survival of patients with locally advanced uterine cervical cancer who were treated with intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration (PPPEC).. Twenty-three untreated patients with stages IIIa-IVa cervical cancer were enrolled in the study. PPPEC was administered twice at 2 weeks interval using high-dose cisplatin alone (140-250 mg/m(2)) or high-dose cisplatin plus mitomycin C (7 mg/m(2)), pepleomycin (7 mg/m(2)) and 5-fluorouracil (700 mg/m(2)). Eighteen patients in whom the tumor downstaging was confirmed underwent radical surgery following PPPEC, whereas in the remaining five patients, radiotherapy was administered.. Two weeks after the second PPPEC, the median volumetric tumor reduction and tumor response were 76% and 87%, respectively. Histologic response was 96%, while the tumor downstaging reached 83%. The curative surgery rate achieved was 89%. Five-year progression-free survival was 47% and 5-year survival rate was 74%.. High-dose intraarterial infusion chemotherapy under PPPEC effectively achieved tumor downstaging and resulted in the favorable performance of the subsequent radical surgery and improved the 5-year survival rate of patients with locally advanced uterine cervical cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Staging; Peplomycin; Uterine Cervical Neoplasms

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

Topics: Adult; Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cricetinae; Female; Humans; Ifosfamide; Magnetic Resonance Imaging; Male; Middle Aged; Peplomycin; Uterine Cervical Neoplasms

This is a retrospective analysis of 55 patients with stage III carcinoma of the uterine cervix treated with radiation from November 1984 through December 1991. Eleven of the patients were treated with radiation and transarterial infusion chemotherapy (TAI), using cis-platinum and pepleomycin. The 3- and 5-year cumulative survival rates for all patients were 61% and 58%, respectively, and the 3-year cumulative survival rate for the group with combined radiation and TAI was 47%. According to initial failure site, the locoregional recurrence rate was 36.8%, and that for para-aortic lymph node metastasis and distant metastasis was 31.6%. The failure pattern was similar between the irradiation only group and the group with combined radiation and TAI. The incidence of intestinal complications of grades 1 and 2 was 20%. Irradiation combined with TAI did not increase the incidence of complications.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Humans; Infusions, Intra-Arterial; Middle Aged; Peplomycin; Prognosis; Retrospective Studies; Uterine Cervical Neoplasms

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Mitomycin; Peplomycin; Uterine Cervical Neoplasms; Vincristine; Vulvar Neoplasms

Based on the fact that combination chemotherapy with cisplatin, ifosfamide, and bleomycin generated a 69% response rate in patients with recurrent cervical cancer; that 254-S (a cisplatin analogue) monotherapy generated a 46.3% response rate for cervical cancer, which was higher than those generated by cisplatin and carboplatin in historic comparison; and that peplomycin is a bleomycin analogue with improved pulmonary toxic effects, a combination regimen with 254-S, ifosfamide, and peplomycin was evaluated in an animal experiment and a clinical study in patients with advanced or recurrent cervical cancer with an expectation that the regimen might show a higher efficacy than 254-S monotherapy and the combination regimen including cisplatin.. In the clinical testing, 254-S was administered intravenously (IV) at 80-100 mg/m2, ifosfamide was administered IV at 1500 mg/patient for 5 days, and peplomycin was administered intramuscularly at 5 mg/patient for 6 days. This treatment was repeated every 4 weeks.. As a result, this regimen showed additive or synergistic antitumor effects in mice receiving B16 melanoma transplants. In the clinical study, 83.8% and 60.9% response rates were obtained in 37 previously untreated patients with Stage III or IV cervical cancer and 23 with recurrent cervical cancer, respectively. The dose-limiting factor was bone marrow toxic effects, which were tolerable. The other toxic effects were mild, and there were no deaths.. From these results, this combination regimen was thought worthy of evaluation in a Phase III comparative study in patients with advanced or recurrent cervical cancer.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Female; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intramuscular; Melanoma, Experimental; Mice; Mice, Inbred Strains; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Organoplatinum Compounds; Peplomycin; Prognosis; Skin Neoplasms; Uterine Cervical Neoplasms

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

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

Cervical adenosquamous carcinoma is a special histological type of cervical carcinoma. Its clinic-pathologic characteristics and prognostic factors have seldom been reported. This study was to explore the clinic-pathologic characteristics and prognostic factors of cervical adenosquamous carcinoma.. Clinical data of 83 pathologically confirmed adenosquamous cervical carcinoma patients in Sun Yat-sen University Cancer Center from Nov. 1982 to May 2006 were analyzed.. The median overall survival (OS) of 83 patients was 47 months and the median disease-free survival was 43 months. The 5-year survival rate was 74.0%, and the recurrence rate (DFS) was 30.1% (25/83). The median OS and DFS were 58 months and 54 months versus 37 months and 21 months in patients with or without lymph node metastasis (P=0.005, P<0.001). The median DFS was 47 months and 16 months for patients with the tumor diameter >4 or < or =4 cm (P=0.015), respectively. Lymph node metastasis was correlated to FIGO stage, tumor diameter and invasion depth. The recurrence rate of patients with ovarian preservation was 33.3% (3/9).. Lymph node metastasis is an independent risk factor for prognosis in cervical adenosquamous carcinoma. Adjunctive postoperative irradiation would improve the OS and DFS. Tumor diameter greater than 4cm is an independent prognostic risk of DFS. The impact of ovarian preservation on prognosis is unclear.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hysterectomy; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Peplomycin; Prognosis; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate; Tumor Burden; Uterine Cervical Neoplasms

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

The study was performed to examine how bleomycin (BLM) and peplomycin (PEM) should be effectively used in radiotherapy for cervical squamous cancer patients.. The effects of BLM on radiosensitivity and the effects of radiation on the sensitivity to BLM of cancer cells were investigated using the radiosensitive human cervical squamous cell carcinoma cell line ME180.. BLM treatment did not affect radiosensitivity. However, irradiation significantly reduced cell BLM sensitivity in a dose-dependent manner. There was no significant difference in BLM sensitivity and PEM sensitivity between cells concurrently irradiated and those treated with BLM or PEM 8 h before or 8 h after irradiation.. Since sensitivity to BLM is reduced during irradiation, BLM should be administered to cervical cancer patients as an adjuvant chemotherapeutic drug after completion of radiotherapy.

Topics: Antibiotics, Antineoplastic; Bleomycin; Cell Line, Tumor; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Neoplasms, Squamous Cell; Peplomycin; Radiation-Sensitizing Agents; Uterine Cervical Neoplasms

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

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

We presented a case of locally advanced cervical cancer treated by intraarterial infusion chemotherapy, and evaluated the blood flow of uterine arteries before and after chemotherapy by using a transvaginal ultrasonic color Doppler device. Pulsatility index (PI) of each uterine artery increased after first course of chemotherapy compared to that of before chemotherapy. But PI did not change after second course in spite of a significant reduction in tumor size. Blood flow change assessed by Doppler ultrasound may be a limited but useful parameter for the efficacy of neoadjuvant chemotherapy in patients with cervical cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Arteries; Chemotherapy, Adjuvant; Cisplatin; Female; Humans; Hysterectomy; Infusions, Intra-Arterial; Lymph Node Excision; Middle Aged; Mitomycin; Peplomycin; Pulsatile Flow; Ultrasonography, Doppler, Color; Uterine Cervical Neoplasms; Uterus

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

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

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

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

By means of re-irradiation using pepleomycin suppository in uterine cavity, we attained local control for one patient who had local recurrence in uterine cavity and suffered from uterine fluor in which viable cancer cells were confirmed. We were enlightened by this therapeutic experience, so we attempted combination therapy using pepleomycin suppositories to supplement intra-cavitary irradiation, for the 11 selected patients who were suffering from uterine fluor. We investigated the treatment results in 7 patients of stage III out of 11 patients (of all stages), in comparison with 13 patients of stage III who were treated by irradiation alone. Consequently, these treatment results were approximately equivalent, and the incidence of sigmoid complications could be decreased. Side effects which were followed by the combination therapy were not serious, and so we believe that pepleomycin suppository is a simple method and valuable to supplement radiation therapy of uterine cervical cancer.

Topics: Administration, Intravaginal; Adult; Aged; Bleomycin; Brachytherapy; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Middle Aged; Peplomycin; Radiotherapy Dosage; Suppositories; Uterine Cervical 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

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

An allergic reaction to peplomycin was observed in a patient with cervical uterine cancer who had previously been treated with peplomycin. A positive Prausnitz-Küstner test and its elimination after heat treatment of the serum showed the production of anti-peplomycin IgE antibody. Peplomycin was coupled to a paper disc and a sensitive radioallergosorbent test for peplomycin was developed to quantitate the antibody. Patient serum IgE and IgG were purified by DE52 column chromatography; the IgE fraction contained binding activity to peplomycin. A competition test revealed that the antibody bound to both peplomycin and bleomycin. DNA, RNA, and mononucleotides had no effect on antibody binding, but the antibody inhibited peplomycin's activity.

Topics: Aged; Antibody Specificity; Bleomycin; Combined Modality Therapy; Cross Reactions; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Immunoglobulin G; Intradermal Tests; Peplomycin; Uterine Cervical Neoplasms

Eighteen patients with advanced or recurrent carcinoma of the cervix were treated with a combination of peplomycin, vincristine, mitomycin-C, and cisplatin (POMP). Ten of the 16 evaluable patients (63%) responded, including 4 with a complete response. Median duration of the response was 7 months. Two of 6 with intrapelvic recurrent tumors responded to some extent following intraarterial infusion. The subcutaneous infusion of peplomycin was well accepted by the patients. Toxicity was tolerable. This regimen seemed to be one of the regimens which should be considered for the advanced or recurrent cervical cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Female; Follow-Up Studies; Humans; Mitomycin; Mitomycins; Peplomycin; Uterine Cervical Neoplasms; Vincristine

As the treatment of inoperable, radioresistant or recurrent cases of uterine cancer (cervical or endometrial) whose lesions were restricted to the pelvis, internal iliac arterial chemotherapy was carried out and its therapeutic results were evaluated. Thirty three cases including 22 primary and 11 recurrent ones were dealt with this study. Among 33 cases, catheter was introduced to the internal iliac artery via superior gluteal artery in 9, inferior gluteal artery in 22 and lateral umbilical artery in 2 cases. Oncostatics, including mainly cisplatin, adriamycin and pepleomycin, were administered via artery daily or once or three times a week with indwelling of the catheter as long as 7 months in average. Eight patients out of 33 were living with average survival time of 18.2 months following the initiation of intra-arterial chemotherapy. Among 27 cases whose therapeutic effects were evaluable histologically, tumor cells had disappeared as long as at least 4 months in 23, within 4 months in 3 cases and tumor cells continued to be present in one case. In 22 primary cases, 3 were living without evidence of disease, one was living with disease and remaining 18 cases were dead due to other diseases in two cases, distant metastasis in 7 cases, troubles of the primary site in 8 cases and unknown reason (septic shock?) in one case. Four of 11 recurrent cases were living with one case of tumor bearing state. Complete response (CR) was obtained in 5 cases and partial response (PR) in 4 among 9 evaluable recurrent cases. As for the recurrent cases whose main therapy was intra-arterial chemotherapy only, CR was gained in 3 and PR was got in 4 out of 7 cases. Severe side effects were observed in 11, moderate one in 15 and mild one in 6 cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Doxorubicin; Drug Evaluation; Female; Humans; Iliac Artery; Infusions, Intra-Arterial; Middle Aged; Peplomycin; Remission Induction; Uterine Cervical Neoplasms; Uterine Neoplasms

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

Seventeen patients with recurrent uterine cervical cancer were treated with combination chemotherapy consisting of consecutive intravenous drip infusion of PEP 5 mg for 6 days and intravenous infusion of MMC 10 mg on the 6th day. Of twelve evaluable cases, 2 complete responses and 6 partial responses were obtained and the response rate was 67%. The median survival for responders was 61.3 weeks as compared with 28.0 weeks for non-responders. The initial clinical effect appeared after at least two courses. Pulmonary toxicity in the form of interstitial pneumonitis occurred in 8 cases (50%) including 2 cases of pulmonary fibrosis. This result suggests that PM therapy is a very useful treatment method for recurrent uterine cervical cancer which can be performed safely.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Middle Aged; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Peplomycin; Uterine Cervical Neoplasms

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

A continuous subcutaneous infusion of peplomycin was performed on 15 patients with cervical cancer. Eight patients received 5 mg of peplomycin a day and 7 patients received 2.5 mg a day. The peplomycin concentrating in the serum after infusion for 24 hours thus were 0.094 microgram/ml and 0.056 microgram/ml, respectively. The concentration of peplomycin in the tumor was found to be higher than in normal cervical tissue, and in the lymph nodes it was equal or higher than in the serum. Histological changes were minimum. A Grade IIa determination, however, was found in one patient, which may have been due to the total dose and/or the time of the examination. No pulmonary toxicity developed in any patients.

Topics: Adult; Aged; Bleomycin; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Middle Aged; Peplomycin; Uterine Cervical Neoplasms

Surgery and radiation therapy are major treatments for carcinoma of the uterine cervix. However, there has been little improvement in survival recently. Since 1982, we have introduced multiagent chemotherapy consisting of cis-platinum, vincristine and peplomycin (CVP) to control systemic disease and to do cytoreduction prior to operation and/or radiation therapy. Our results are as follows. Thirty-one patients have been treated with CVP. Among eleven patients initially treated with CVP, 7 patients responded well to this regimen alone, including three patients who entered complete clinical remission. This indicates that this regimen is effective against carcinoma of the uterine cervix. Two patients who were thought to be candidates for radical hysterectomy became able to have less extensive surgery following CVP treatment. It is difficult for this CVP combination to control bulky tumors within previously radiated fields, probably because of poor vascularity due to pelvic fibrosis caused by radiation. Metastatic disease were also able to be controlled by this combination especially in two patients with pulmonary metastases. Nausea, vomiting and mild myelosuppression were frequently encountered, but they were tolerated well by the patients. However, great care must be taken in using peplomycin when the cumulative dose becomes large.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Female; Humans; Middle Aged; Peplomycin; Postoperative Period; Uterine Cervical Neoplasms; Vincristine

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: Bleomycin; Cervix Uteri; Combined Modality Therapy; Female; Humans; Peplomycin; Radiation-Sensitizing Agents; Suppositories; Tissue Distribution; Uterine Cervical Neoplasms

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

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

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

Based on Peplomycin-induced cell cycle distribution analyzed by a flow-cytemetry using HeLa S-3 and SNG-M cells in vitro, we investigated reasonable periods and kinds of drug combined with pepleomycin (PEP). Changes in both the PEP treatment time and dosage produced a redistribution which decreases the number of cells in the G1 phase and increased the number of cells in the S and G2-M phases. The period with the maximum number of cells in the S phase was 12 hours in the HeLa S-3 and 16 hours in the SNG-M and, that in the G2-M phases, 16 hours in the HeLa S-3 and 22 hours in the SNG-M after the treatment. In the combination of the pep with CIS-DDP 4-hydroperoxy cyclophosphamide Adriamycin (ADR) and ACNU, the cytotoxic potency of the four drugs were CIS-DDP greater than 4-Hydroperoxy cyclophosphamide greater than ADR greater than ACNU in the HeLa S-3 and 4-Hydroperoxy cyclophosphamide greater than CIS-DDP greater than ADR greater than ACNU in the SNG-M. This suggests that the Cis and 4-Hydroperoxy cyclophosphamide were adequate for the combination with the PEP. The period of the combination should be at the time of the greatest accumulation of cells in the G2-M phase, because the pep effectively produced the G2-M partial synchronization. These results suggest that the combination chemotherapy should be based on the analysis of the cell cycle.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Line; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Flow Cytometry; Humans; In Vitro Techniques; Interphase; Nimustine; Nitrosourea Compounds; Peplomycin; Uterine Cervical Neoplasms; Uterine Neoplasms

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

Various types of human gynecological cultured tumor cells were tested for the sensitivity to Peplomycin (PEP), an effective antitumor antibiotic for squamous cell carcinomas, by the regrowth assay method together with morphological observation. Bleomycin-hydrolase activity of these cell lines was also compared in cell-free extracts by assaying the conversion of Bleomycin into its deamidated from (HPLC method). SKG-I, SKG-II, SKG-IIIb cells derived from squamous cell carcinoma of the cervix and RKN cells derived from myosarcoma of the ovary were much more sensitive to PEP than other cell lines. PEP was found to be mainly a time-dependent drug, but also concentration dependent. The effect of PEP on cell morphology was characterized by the appearance of enlarged cells and swelling nuclei. The specific activities of Bleomycin-hydrolase in SKG-I, SKG-II, SKG-IIIb cells were shown to be relatively lower than that in other cell lines. These results suggested that cervical squamous carcinoma cells and ovarian myosarcoma cells were sensitive to PEP and Bleomycin-hydrolase activity was one of factors which decided the PEP sensitivity of human cultured tumor cells.

Topics: Antibiotics, Antineoplastic; Bleomycin; Cell Division; Cell Line; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Drug Resistance; Female; Genital Neoplasms, Female; Humans; Ovarian Neoplasms; Peplomycin; Uterine Cervical Neoplasms; Uterine Neoplasms

In the search for bleomycin analogues with less pulmonary toxicity than bleomycin itself, peplomycin was selected for a phase I clinical trial, based on experimental animal data. Eighteen patients received peplomycin at three exploratory levels. Six patients were treated at a level of 5 mg/m2, 8 patients at 10 mg/m2 and 4 patients at 15 mg/m2 of peplomycin, each dosage being given twice weekly intravenously. Pulmonary function tests were performed prior to treatment and serially thereafter. Pulmonary toxicity was encountered when the administered total dose of peplomycin was in the range 190-350 mg in patients who had received either 10 or 15 mg/m2 twice weekly. Pulmonary toxicity was not observed when the dosage of peplomycin was restricted to 5 mg/m2 twice weekly. During the trial no haematological, hepatic or renal changes induced by the drug were observed. Skin changes, stomatitis and fever were observed with increasing frequency the higher the cumulative dose of peplomycin, and these effects were similar to those seen with bleomycin. Two of fifteen patients with cervical cancer obtained a partial response, lasting 1 and 2 months respectively. Although peplomycin is free from pulmonary toxicity at a dose of 5 mg/m2 twice weekly, the maximum tolerated cumulative dose has still to be defined.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Kidney Neoplasms; Lung Diseases; Middle Aged; Ovarian Neoplasms; Peplomycin; Respiratory Function Tests; Skin Diseases; Uterine Cervical 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

Five cases of recurrent cervical carcinoma with restricted recurrent site in the pelvis were treated with intra-arterial infusion of oncostatics via the internal iliac artery. The tip of the catheter was put in the internal iliac artery, just proximal to the superior glutea artery, through the a. glutea inferior or superior with ligation of both the a. glutea superior and inferior so as to get a high concentration of drugs at the lesion. Several chemotherapeutic agents, such as Cisplatin, adriamycin, pepleomycin, mitomycin C and 5-FU, were infused through the other end of the catheter, which was fixed at the subclavian fossa of the anterior chest. The clinical efficacies according to Karnofsky's criteria were 0-C in one case, 1-A in 1 case and 1-B in 3 cases. The overall response rate above 1-B was 60%. Two cases were dead, one due to inflammation in the pelvic dead space and D.I.C. and other due to myocarditis and heart failure. The other three were alive and treated with weekly intra-arterial infusion at our outpatient clinic. No troubles, such as spontaneous removal of the catheter, inflammation around the catheter or bleeding, have been encountered. The toxicities in the case of intra-arterial infusion were less prominent than in the case of intravenous administration of the same dosage of the oncostatics.

Topics: Antineoplastic Agents; Bleomycin; Cisplatin; Doxorubicin; Drug Therapy, Combination; Female; Humans; Infusions, Intra-Arterial; Middle Aged; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Peplomycin; Uterine Cervical Neoplasms

Five cases of recurrent cervical carcinoma with sites of recurrence restricted to the pelvis were treated by intra-arterial infusion of oncostatics via the bilateral internal iliac arteries. One tip of the catheter was positioned in the internal iliac artery, proximal and close to the superior glutea artery, through the arteria glutea superior or inferior with ligations of both arteria glutea superior and inferior so as to give high concentration of drugs in the lesion. The other tip of the catheter was introduced subcutaneously up to the subclavian fossa of the anterior chest and was secured to the skin. Several chemotherapeutic agents (cisplatin, adriamycin, pepleomycin, mitomycin C and 5-fluorouracil) were infused repeatedly through the catheter, once or twice a week. The clinical efficacy according to Karnovsky's criteria was 0-C in one case, 1-A in one case and 1-B in three cases. The overall response rate of 1-B or higher was 60%. Two patients died, one from inflammation in the pelvic dead space and disseminated intravascular coagulopathy, the other from myocarditis and heart failure. The other three are alive and being treated by weekly intra-arterial infusion of chemotherapeutic agents at our outpatient clinic. No problems, such as spontaneous removal of the catheter, inflammation around the catheter or bleeding, have been encountered. The toxicity of the oncostatics in case of intra-arterial infusion was less pronounced than in the case of intra-venous administration of the same dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Catheterization; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Humans; Hysterectomy; Iliac Artery; Infusions, Intra-Arterial; Lymphatic Metastasis; Middle Aged; Mitomycin; Mitomycins; Pelvic Neoplasms; Peplomycin; Recurrence; Uterine Cervical Neoplasms

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