Oral combination chemotherapy in conjunction with filgrastim (G-CSF) in the treatment of AIDS-related non-Hodgkin's lymphoma: evaluation of the role of G-CSF; quality-of-life analysis and long-term follow-up.

In 1993 we reported the efficacy and toxicity profile of an oral combination regimen administered to 18 patients with AIDS-related lymphoma (NHL-1 study). We observed a 61% response rate; 39% one-year survival rate; nearly two-thirds of patients developed > or = grade 3 leukopenia; and 28% of cycles were associated with febrile neutropenia. These results prompted us to shorten the duration of therapy and to add G-CSF to ameliorate the myelosuppression. Twenty patients with biopsy-proven AIDS-related lymphoma were treated with three 6-week cycles of oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, cycles no. 1 and 3; etoposide 200 mg/m2 days 1-3; cyclophosphamide and procarbazine both 100 mg/m2 days 22-31; and G-CSF 5 microg/kg subcutaneously days 5-21 and days 33-42 (NHL-2 study). The following analyses were undertaken: (1) evaluation of toxicity and efficacy parameters for patients in the current (NHL-2) study; (2) analysis of the clinical role of G-CSF by (historical) comparison with the NHL-1 study of the same regimen without G-CSF; (3) quality-of-life assessments using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments for all 38 patients (NHL-1+2); and (4) long-term follow-up for all 38 patients. In the current study the overall objective response using ECOG criteria was 70% (95% CI, 50-90%) with 6 CRs (30%) and 8 PRs (40%). The median survival duration was 7.3 months (range: 0.5-51+ months). One patient developed CNS relapse. There were no significant differences with respect to demographics or prognostic factors between the patient populations of the NHL-1 study and the current study (P > 0.2 for each factor). Myelosuppression was the major toxicity in both studies. In the current study versus the NHL-1 study, although the lower incidences of grade 3/4 myelosuppression (51% vs. 64%) and febrile neutropenia (17% vs. 28%) on a per cycle basis were not statistically significant, fewer patients (40% vs. 60%) were affected. However, the severity of myelotoxicity was lessened with the addition of G-CSF, measured in terms of the discontinuation of therapy, myelotoxic deaths, and freedom from grade 3/4 myelotoxicity ( P < 0.02). The number of hospitalizations for febrile neutropenia (7 in the NHL-2 study vs. 13 in the NHL-1 study) was also significantly different (P < 0.05). Quality-of-life analysis confirmed no significant functional or psychological deterioration during therapy except for patients experiencing febrile neutropenia, whose functional capacity deteriorated (P < 0.04). The 1-year, 18-month, and 2-year survival rates for the combined studies (38 patients) were 32%, 21%, and 13%, respectively. At time of death 49% of patients were free from progression of their lymphoma. Administration of the oral regimen has resulted in 13% of patients surviving two years, and half of patients surviving free from progression of their lymphoma. This regimen is efficacious and considerate of patient quality-of-life issues. The addition of G-CSF to the regimen decreases the frequency of hospitalization for febrile neutropenia.

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.