peplomycin and nedaplatin

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

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

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

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