Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients
C Dumontet1, J Jaubert, C Sebban
1Service d'Hématologie, CHU de Pierre Bénite, Lyon, France. charles.dumontet@chu-lyon.fr
Background:
Patients with relapsing or refractory multiple myeloma have poor prognosis. Few compounds are active in these patients and response duration remains short. We report the results of an open phase II trial evaluating the efficacy and safety of fotemustine monotherapy.
Patients And Methods:
Twenty-one patients with relapsing (17) or refractory (four) multiple myeloma received fotemustine 100 mg/m(2) on an outpatient basis on days 1 and 8 of the induction cycle, followed after a 6-week rest period by fotemustine 100 mg/m(2) every 3 weeks until progression or unacceptable toxicity. Fotemustine pharmacokinetics during the first day of induction was compared between patients with normal or abnormal renal function.
Results:
Five of 20 eligible patients had an objective response giving an intention-to-treat response rate of 25% [95% confidence interval (CI) 6% to 44%] and a 35.7% response rate (95% CI 11% to 61%) in the 14 patients having received at least four injections of fotemustine. The median time to objective response was 8.9 months. The median times to progression and survival were 13.8 and 23.1 months, respectively, with a 2-year survival rate of 49%. The main toxicity was myelosuppression with grade 3-4 neutropenia and thrombocytopenia in 66% and 71% of patients, respectively. There was one toxic death by sepsis after induction. The pharmacokinetic parameters in renal-impaired patients were not significantly different from those in patients with normal renal function with a similar incidence of grade 3-4 toxicity in both groups.
Conclusions:
Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment.
Insights
Fotemustine shows activity in relapsing or refractory multiple myeloma patients. This agent is safe for patients with mild to moderate renal impairment, offering a new treatment option.
Area of Science:
- Oncology
- Hematology
- Clinical Pharmacology
Background:
- Relapsing or refractory multiple myeloma presents a poor prognosis with limited effective treatment options and short response durations.
- There is a critical need for novel therapeutic agents in this patient population.
Purpose of the Study:
- To evaluate the efficacy and safety of single-agent fotemustine in patients with relapsing or refractory multiple myeloma.
- To assess fotemustine pharmacokinetics and toxicity in patients with varying renal function.
Main Methods:
- An open-label, phase II trial involving 21 patients with relapsing or refractory multiple myeloma.
- Patients received fotemustine 100 mg/m(2) on days 1 and 8, followed by 3-weekly doses until progression or toxicity.
- Pharmacokinetic analysis compared patients with normal versus impaired renal function.
Main Results:
- An intention-to-treat response rate of 25% was observed; 35.7% in patients receiving at least four injections.
- Median time to progression was 13.8 months, and median survival was 23.1 months, with a 2-year survival rate of 49%.
- Myelosuppression (neutropenia and thrombocytopenia) was the primary toxicity; renal function did not significantly impact pharmacokinetics or toxicity.
Conclusions:
- Fotemustine demonstrates definite activity as a single agent in relapsing or refractory multiple myeloma.
- The drug exhibits acceptable toxicity and can be safely administered at conventional doses in patients with mild to moderate renal impairment.
