(ChemotherapyAdvisor)–Neoadjuvant topotecan plus cisplatin (TOPOCIS) chemotherapy is a promising alternative to radiotherapy or chemoradiotherapy for locally-advanced cervical cancer treatment, according to a multicenter Phase 2 toxicity and efficacy study published in the European Journal of Cancer.
Weekly topotecan plus cisplatin “showed promising efficacy and very acceptable toxicity profile in locally advanced cervical cancer,” reported lead author Flavia Zanaboni, MD, of the Gynecologic Oncology Unit, IRCCS Istituto Nazionale dei Tumori Foundation in Milan, Italy, and coauthors.
A total of 92 patients, with a mean age of 49 years, diagnosed with squamous or adenosquamous cervical cancer were enrolled in the trial between November 2008 and January 2011. Participants received 6 courses of weekly topotecan (2mg/m2) and cisplatin (40 mg/m2).
At a median follow-up of 18 months, 24% of patients had relapsed and 13% had died; 76% had not experienced recurrence. The clinical response rate was 77% (95% CI, 68%-86%), including 7 complete responses (8%) and 64 partial responses (69%), the authors reported. Progression was observed in 9 patients (10%); these patients underwent definitive radiotherapy ± chemotherapy.
“The therapy was generally well tolerated; 96% of patients completed the planned 6 courses, and 95% of them were administered without interruption or delay and at a full dose,” the authors noted.
Grade 3-4 adverse events occurred in 28% of patients. Grade 3-4 neutropenia occurred in 25% of patients; Grade 3-4 anemia in 7%; and 1% of patients experienced Grade 3-4 thrombocytopenia. The majority (93%) of severe toxicities emerged after the third course of treatment, the authors reported.
“We observed persistent amenorrhea during chemotherapy in 21% of patients in the reproductive age, with regular menstrual periods at baseline” the authors noted.
No treatment-related deaths or severe neurologic toxicities were observed.
“Supportive therapies, including blood transfusions, G-CSF and erythropoietin were given to 24% of patients, only in cases of long-lasting severe toxicity,” they noted.
Eligibility criteria included Stage IB2, IIA, or IIB, with Eastern Cooperative Oncology Group (ECOG) Performance Status scores of ≤2; neutrophils ≥ 1,500/µL; platelets ≥ 100,000/µL; and normal kidney and liver function, the authors reported.
Neoadjuvant systemic chemotherapy prior to has “several potential advantages over conventional treatment,” the authors noted – including down-staging improving the success rate of resection, “eradication of micrometastases,” and reduced toxicity, the authors wrote.