Multi‐institutional phase II study of neoadjuvant irinotecan and nedaplatin followed by radical hysterectomy and the adjuvant chemotherapy for locally advanced, bulky uterine cervical cancer: A Kansai Clinical Oncology Group study (KCOG‐G1201)

Abstract

Aim: A multi-institutional phase II trial was conducted to determine the efficacy and toxicity of neoadjuvant chemotherapy with irinotecan and nedaplatin followed by radical hysterectomy and adjuvant chemotherapy for locally advanced, bulky stage IB2-IIB cervical cancer. Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB2-II, bulky type (>4 cm in diameter) squamous cell carcinoma of the uterine cervix were enrolled. Irinotecan (60 mg/ m 2 ) was administered intravenously on days 1 and 8 and nedaplatin (80 mg/m 2 ) was also administered on day 1 of every 21-day cycle. After two cycles of chemotherapy, a radical hysterectomy was performed. Until 6 weeks after the surgery, three to five cycles of the regimen were added as adjuvant chemotherapy. The primary endpoint was the 2-year relapse-free survival rate. The response rates and toxicities were evaluated as secondary endpoints. Results: Thirty-two patients from seven institutions were enrolled in this study. The median age was 48 years (range 25-75 years). The average follow-up period was 37.8 months (15-71 months). Twenty-three patients completed the regimen as planned. The objective response rate (complete response + partial response) for the neoadjuvant chemotherapy regimen was 81.2%. The 2-year and 5-year relapse-free-survival rates were 87.5% and 78.8%, respectively. The incidence of grade 3/4 neutropenia was 6.3% and 34.4% during neoadjuvant and adjuvant treatment, respectively. All other toxicities were well tolerated. Conclusion: Our treatment showed efficacy and tolerability for patients with locally advanced, bulky stage IB2-IIB cervical cancer. This suggests that treatment has the potential to improve the prognosis compared to concurrent chemo-radiotherapy.

Paclitaxel Plus Platinum Neoadjuvant Chemotherapy Followed by Surgery Versus Primary Surgery in Locally Advanced Cervical Cancer—A Propensity Score Matching Analysis

“…However, patients who accepted BOMP (cisplatin, vincristine, bleomycin, mitomycin) regimen in the phase III clinical trial-JCOG0102 showed 66% overall response, 41% severe leukopenia, and 27% severe thrombocytopenia (18). In a recent phase II clinical trial, Mori et al (28) evaluated the efficacy of irinotecan combined with nedaplatin in neoadjuvant chemotherapy: with 81.2% overall clinical response, the incidence of severe leukopenia was as high as 40.7%. Therefore, TP/TC regimen is with high response and rare adverse reaction, which is superior to other regimens for neoadjuvant chemotherapy.…”

“…In a recent phase II clinical trial, Mori et al. ( 28 ) evaluated the efficacy of irinotecan combined with nedaplatin in neoadjuvant chemotherapy: with 81.2% overall clinical response, the incidence of severe leukopenia was as high as 40.7%. Therefore, TP/TC regimen is with high response and rare adverse reaction, which is superior to other regimens for neoadjuvant chemotherapy.…”

UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy

“…Takekuma et al reported that chemotherapy after surgery for high-risk patients had similar e cacy and a different toxicity pro le from that of CCRT, associated with worse toxicity than chemotherapy [9]. In Japan, phase II trials have been conducted to determine the e cacy and toxicity of neoadjuvant chemotherapy (NAC) with irinotecan (CPT-11) and nedaplatin (NDP) followed by radical hysterectomy and adjuvant chemotherapy for locally advanced, bulky stage IB2-IIB cervical cancer [10][11][12][13].…”

UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study

“…Takekuma et al reported that chemotherapy after surgery for high-risk patients had a similar efficacy but a different toxicity profile than that of CCRT, which is associated with worse toxicity than chemotherapy [ 9 ]. In Japan, phase II trials have been conducted to determine the efficacy and toxicity of neoadjuvant chemotherapy (NAC) with irinotecan (CPT-11) and nedaplatin (NDP) followed by radical hysterectomy and adjuvant chemotherapy for locally advanced, bulky stage IB2-IIB cervical cancer [ 10 – 13 ]. Postoperative chemotherapy with CPT-11 and NDP without radiotherapy was also found to be very effective in high-risk patients with node-positive cervical cancer [ 14 ].…”