Phase I study of combination chemotherapy with irinotecan hydrochloride and nedaplatin for cervical squamous cell carcinoma: Japanese gynecologic oncology group study

Abstract

Abstract. The aim of this study (JGOG1063) was to determine the recommended dose (RD) for combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (NDP) for advanced cervical squamous cell carcinoma. CPT-11 was given intravenously in fixed doses of 60 mg/m 2 on days 1 and 8 and NDP, in escalating doses, on day 1, every 4 weeks. A total of 15 patients were enrolled in the study. At level 1 (NDP: 50 mg/m 2 ), one of the 3 patients developed grade 3 diarrhea, so 3 additional patients were enrolled at this level. As none of the 3 additional patients exhibited dose-limiting toxicity, level 1 was elevated to level 2 (NDP: 60 mg/m 2 ). The maximum tolerated dose was not reached, even at the highest dose level (level 4; NDP: 80 mg/m 2 ). No further dose escalation was carried out, and level 4 (CPT-11: 60 mg/m 2 , NDP: 80 mg/m 2 ) was determined as the RD.

Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies

“…In the current study, the average NDP dose calculated by BSA was 63.9 mg/m 2 at level 1, 74.3 mg/m 2 at level 2, and 86.1 mg/m 2 at level 3, and the dose was gradually increased by AUC. The JGOG phase I study suggested that the recommended doses of CPT-11 (days 1 and 8) and NDP (day 1) were 60 and 80 mg/m 2 , respectively [13]. In three patients with DLT, the doses of NDP that were calculated by BSA were 55.9, 68.6, and 96.1 mg/m 2 , suggesting that the relatively low NDP dose that was calculated by BSA might induce severe toxicity.…”

“…The Japanese Ministry of Health, Labour and Welfare recommended the administration of NDP alone at doses of 80-100 mg/m 2 every 28 days. The phase I study conducted by the Japanese Gynecologic Oncology Group (JGOG) indicated that the recommended doses of CPT-11 (days 1 and 8) and NDP (day 1) were 60 and 80 mg/m 2 , respectively [13]. A previous study found that 27.6 % of patients received NDP at doses of 60-80 mg/m 2 , 45.2 % received NDP at doses of 80-100 mg/m 2 , and 24.0 % received a dose of more than 100 mg/m 2 for the dose of NDP at AUC 12 [14].…”

Nedaplatin and irinotecan combination therapy is equally effective and less toxic than cisplatin and irinotecan for patients with primary clear cell adenocarcinoma of the ovary and recurrent ovarian carcinoma

“…In a phase I study, the Japanese Gynecologic Oncology Group (JGOG) established a recommended dose for patients with cervical carcinoma patients. A phase II study investigating its use as postoperative adjuvant chemotherapy for cervical carcinoma is currently being performed (19). Few available reports regarding the use of NDP/CPT for ovarian carcinoma are available; however, one study showed CR to NDP/CPT in patients with CCC metastasis to the common iliac lymph node (16).…”

“…NDP/CPT has been used as chemotherapy for lung, cervical, and testicular carcinomas (12,(19)(20)(21). In a phase I study, the Japanese Gynecologic Oncology Group (JGOG) established a recommended dose for patients with cervical carcinoma patients.…”

Factors affecting platinum sensitivity in cervical cancer

“…Thus, NDP is associated with a high response rate in cervical cancers that is comparable to the response rate achieved with cisplatin. In addition, NDP has fewer gastrointestinal side effects, is less nephrotoxic and requires less additional fluid during infusion (10,11). For this reason, NDP has been widely used in Japan for the treatment of cervical cancer and was the agent selected for the present HDRA chemosensitivity analysis.…”