Weekly topotecan and cisplatin (TOPOCIS) as neo-adjuvant chemotherapy for locally-advanced squamous cervical carcinoma: Results of a phase II multicentric study

OBJECTIVES: The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer. PATIENTS AND METHODS: From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤ 2; neutrophils ≥1500/μL; platelets ≥100,000/μL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy. RESULTS: Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18 months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died. CONCLUSIONS: Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation