Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID) – a phase II study

Abstract

Purpose: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL) are in the older age groups and are thus less able to tolerate aggressive treatment. Chlorambucil, alone and in combination, has been widely accepted as the initial treatment of choice for many years. The availability of an anthracycline which could be given orally in combination with chlorambucil and steroid led us to investigate the efficacy and toxicity of this novel regimen. Methods: Patients (age less than 70 years) with a histologically confirmed diagnosis of LGNHL (Kiel classification) were eligible for the study if they had no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/m² daily for 3 days given on each day in three divided doses, idarubicin 10 mg/m² for 3 days before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were given orally. Treatment was repeated every 21 days for a maximum of six courses. The regimen was assessed for toxicity and response. Results: A total of 72 patients were registered, and 64 were eligible (median age 52 years). Toxicity was assessed for all cycles given (347). The predominant toxicity was haematological, but in only one course did grade 4 neutropenia (less than 0.5 × 10⁹) occur. Alopecia was not a problem. Full doses of the treatment were administered to 40% of the patients, with no delays or dose reductions. The overall response rate was 83%. Six patients had static disease and two progressed on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of response to treatment. Of 12 patients documented to have raised LDH, 5 failed to respond to treatment, compared to 1 of 32 patients who had a normal LDH (χ² 10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial 5-year event-free survival was 22% and overall survival was 65%. However, in patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for Low Grade Disease) overall survival are 88% and 64%, respectively. Conclusions: This novel regimen was effective and well tolerated.