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Ambamustine in the second-line treatment of patients with small-cell lung cancer: a phase II Fonicap study
A Ardizzoni1, G Antonelli, S Ricci
1Department of Medical Oncology, Istituto Nazionale Ricerca Cancro Genoa, Italy.
Abstract:
Despite a high probability of response to first-line chemotherapy, most patients with small-cell lung cancer (SCLC) will eventually have progression of their disease because of the development of resistant disease. Second-line testing of new drugs is an accepted research strategy in SCLC. In this context, the Italian Lung Cancer Task Force (FONICAP) has tested a new synthetic bifunctional alkylating agent, Ambamustine, with preliminary evidence of activity in other solid tumors. Patients with measurable SCLC, progressive after one first-line chemotherapy regimen (either "sensitive" or "refractory"), were eligible for the study. Ambamustine was administered at the dose of 2 mg/kg as a 1-hour intravenous infusion on day 1 every 21 days. The dose was to be increased to 3 mg/kg if no grade IV toxicity and complete hematologic recovery had occurred by day 22. Sample size was calculated according to a two-stage optimal Simon's design. Seventeen patients were entered into the study. Twelve patients were refractory to prior chemotherapy; 12 had extensive disease; the median age was 64 years (range: 46-75 years) and the median performance status was 1. Among 13 patients who received more than one cycle, 9 patients could increase Ambamustine dose from 2 to 3 mg/kg. No objective response was observed: one patient obtained a 50% regression of the primary tumor with contemporary disease progression in the liver and was qualified as having progressive disease. The treatment was well tolerated: grade IV leukopenia occurred in only 1 patient; grade III anemia occurred in 17.6%, grade III leukopenia in 11.8%, and grade III thrombocytopenia in 23.5%. Nonhematologic toxicity was minimal. Ambamustine, at the dose and schedule used in this study, is well tolerated in pretreated patients with SCLC but has no significant antitumor activity in this unfavorable group of patients.
Insights
Ambamustine, a new chemotherapy drug, was tested in patients with advanced small-cell lung cancer (SCLC) who had disease progression after initial treatment. The drug was well-tolerated but showed no significant anti-cancer activity in this patient group.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Small-cell lung cancer (SCLC) frequently develops resistance to first-line chemotherapy.
- Second-line treatment strategies are crucial for managing SCLC progression.
- Ambamustine, a synthetic bifunctional alkylating agent, has shown preliminary activity in other solid tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of Ambamustine as a second-line treatment for patients with small-cell lung cancer.
- To determine the optimal dose escalation for Ambamustine based on toxicity.
Main Methods:
- A two-stage optimal Simon's design was used to assess Ambamustine's activity.
- Eligible patients had measurable SCLC with disease progression after one prior chemotherapy regimen.
- Ambamustine was administered intravenously, with dose escalation from 2 mg/kg to 3 mg/kg based on toxicity.
Main Results:
- No objective tumor response was observed in any of the 17 patients treated.
- One patient experienced a partial response of the primary tumor but had concurrent liver progression.
- The treatment was generally well-tolerated, with minimal non-hematologic toxicity and manageable hematologic side effects.
Conclusions:
- Ambamustine, at the tested dose and schedule, is well-tolerated in pretreated SCLC patients.
- The drug demonstrated no significant antitumor activity in this unfavorable patient population.
- Further research into novel therapeutic strategies for resistant SCLC is warranted.