Phase I-II trial of irinotecan (CPT) and cisplatin (P) as concurrent chemo-radiotherapy (CCRT) for patients (pts) with primary local advanced cervical cancer (LACC): A KCOG 0328 trial

Abstract

15002 Background: Though CCRT based on P is now recommended in LACC, there is no standard regimen. We conducted a phase I-II trial of CPT and P as CCRT in pts with primary LACC. Methods: Eligibility criteria: histologically confirmed primary LACC as FIGO stage III to IVb by para-aortic lymphnode (PAN) metastasis, age 16–75 years, ECOG performance status <2, adequate bone marrow, hepatic and renal function, and written informed consent. Radiotherapy (RT) consisted of external beam 5040cGy in 28 fractions followed by single application brachytherapy, delivering 1800–2400 cGy to point A in 3–4 fractions. The doses of chemotherapy (CT) were set up as follows: dose level (DL) 0; CPT 20 mg/m2, P 30 mg/m2, DL1; CPT 25mg/m2, P 30 mg/m2, DL2; CPT 30 mg/m2, P 30 mg/m2, and the starting level was chosen DL1. CT was curried out weekly 5 cycles concurrently with RT. Toxicities were assessed according to NCI-CTC ver2.0J and responses were assessed according to RECIST. Results: So far 9 pts have been entered. The median age was 52 years (range 29 -73). All pts were FIGO stage IIIb and histrogically squamous cell carcinoma. Among the first 2 pts in DL1, 2 dose-limiting toxicities (DLT) were observed (delay of treatment due to grade 3 diarrhea and nausea) resulting in dose reduction to DL0. In the next 3 pts in DL0, no DLTs were observed and the study is ongoing as phase II. All pts were evaluable for response and toxicity. Eight complete (CR) and 1 partial response (PR) were seen at target region of cervix. But 2 pts showed progressive disease (PD) at non-target region of PAN, lung and liver, then overall response rate assessed by RECIST was 77.8% (CR 7, PD 2). Now the median follow up period is 16 months (range 6 -30). So far 2 pts of PD died and 3 pts relapsed. The median survival time is 10+ months (range 6+ -30+). Toxicity in DL0 was observed febrile neutropenia in 1 pt only. Conclusions: The CCRT with CPT and P in DL0 is feasible and shows promising activity in pts with primary LACC. No significant financial relationships to disclose.