Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065)

Abstract

The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma. Eligibility included patients who received irinotecan (60 mg/m2) on days 1 and 8 and nedaplatin (80 mg/m2) on day 1 of a 21-day cycle. After 1-3 courses of chemotherapy, radical hysterectomy was performed. Sixty-eight patients were enrolled. Sixty-six were included in the full analysis set. Their median age was 47 years (range 22-71), the FIGO stage was Ib2 in 18 patients, IIa in 10, and IIb in 38. Radical hysterectomy was performed after NAC in 63 patients (95.5%). The number of administered courses of NAC was 1 in 13 patients, 2 in 43, and 3 in 10. The response rate, the primary endpoint of this study, was 75.8% (CR in 2 patients, PR in 48, SD in 12, PD in 0, and NE in 4). The mean number of treatment courses required for a response was 1.42 (1 course in 30 patients, 2 courses in 19, and 3 courses in 1). The incidences of grade 3 or 4 hematological toxicities were: neutropenia 72.2%, leukopenia 16.7%, anemia 13.6%, thrombocytopenia 7.6%, febrile neutropenia 1.5%, and elevations of alanine aminotransferase and aspartate aminotransferase 1.5%. Grade 3 or 4 non-hematologic toxicities were as follows: diarrhea 6.1%, nausea 3%, anorexia 1.5%, vomiting 1.5%, fever 1.5%, allergic reactions 1.5%, ileus 1.5% and vesicovaginal fistula 1.5%. Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix.

Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma

“…Postoperative pathological examination confirmed that there were no cancer cells in the resected tissues. Yamaguchi et al (21) treated stage IB2 and IIB cervical cancer with irinotecan and nedaplatin, with good therapeutic efficacy. Other studies suggested that the vagina and the cervix are lined with the same type of squamous cell epithelium, and several risk factors are shared by cervical and vaginal carcinoma.…”

Case of pure ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin but responsive to monotherapy with weekly irinotecan

“…The topoisomerase inhibitor irinotecan is a semi‐synthetic derivative of camptothecin that is converted to an active form (SN‐38). Several trials have demonstrated the clinical efficacy of irinotecan against platinum‐resistant epithelial ovarian cancer; moreover, a recent study indicated that irinotecan was active against SCC of the uterine cervix . Several dosing schedules for irinotecan have been established with the goal of maximizing the anti‐tumor effect while minimizing adverse effects.…”

Nedaplatin: a cisplatin derivative in cancer chemotherapy

“…The incidence of grade 3/4 hematologic toxicity was 16.7% for neutropenia, 18.4% for anemia, and 2.0% for febrile neutropenia, but there was no grade 3/4 thrombocytopenia. The Japanese Gynecologic Oncology Group evaluated the efficacy and safety of combination chemotherapy comprising irinotecan 60 mg/m 2 on days 1 and 9 and nedaplatin 80 mg/m 2 every three weeks as neoadjuvant chemotherapy for patients with stage IB2–IIB uterine cervical squamous cell carcinoma 40. The response rate was 75.8%, which included two patients with a complete response, 48 with a partial response, 12 with stable disease, and 0 with progressive disease, with four patients not evaluated.…”