ANGERS, FranceFludarbine (Fludara) and mitoxantrone(Drug information on mitoxantrone) (Novantrone) increased the 1-year complete remission rate in indolent lymphomas to 55%, compared with 11% using CHEP (doxorubicin, cyclophosphamide(Drug information on cyclophosphamide), vindesine(Drug information on vindesine), prednisone(Drug information on prednisone)) in a multicenter European study reported at the ASH meeting.
Charles Foussard, MD, of Centre Hospitalier Universitaire, and his associates in the GOELAMS Group compared the two regimens in patients with advanced low-grade non-Hodgkins lymphomas (NHL).
Patients were 55 to 75 years old, with newly diagnosed, previously untreated NHL. Patients had stage II bulky, stage III, or stage IV disease and at least one adverse prognostic factor, such as B symptoms or a large tumor mass. Mantle cell lymphoma was excluded.
Patients were randomized to receive either fludarabine/mitoxantrone (FM) or CHEP (see Table). In both arms, patients were to undergo monthly courses of treatment for 6 months, then treatment every other month for 6 months, for a total of nine courses over 1 year.
Prophylaxis for Pneumocystis carinii pneumonia (PCP) and herpes zoster was mandated for patients on FM.
Dr. Foussard reported that 75 of the 100 registered patients are now evaluable for response at 6 months and that 53 are evaluable for response at 1 year and for toxicity. Median follow-up is 19 months.
At 6 months, CR, PR, and failure rates for the FM arm were 42%, 48%, and 10%, compared with 9%, 54%, and 37% for the CHEP arm (P = .0008).
Responses at 1 Year
At 1 year (ie, after nine courses of treatment), CR, PR, and failure rates for the FM arm were 55%, 30%, and 15% vs 11%, 39%, and 50% for CHEP (P = .003). (Dr. Foussard noted that this is lower than CHEP response rates reported in previous studies.)
Myelosuppression was the most frequent side effect observed on either regimen. Dr. Foussard reported that FM was discontinued in two patients due to hemolysis and thrombocytopenia, and that almost all patients on FM experienced severe lymphocytopenia.
Three cases of local herpes zoster were seen: one with CHEP, two with FM. There were no cases of PCP and no toxicity-related deaths. During the discussion, Dr. Foussard said that one or two patients on each arm transformed to large-cell disease.
Dr. Foussard was also asked about the doxorubicin(Drug information on doxorubicin) dose. This trial used 25 mg/m², although 50 mg/m² is more common. He said that the investigators felt that the lower dose is as good as the higher dose for this type of NHL.
These results confirm the efficacy of FM for untreated patients with low-grade NHL, Dr. Foussard concluded. Prophylactic antibiotics may explain the rarity of opportunistic infections, especially PCP. The FM combination seems a promising new regimen for patients with indolent lymphoma.
He also pointed out that this study shows that FM may be used safely in elderly patients as first-line therapy, since patients ranged in age up to 75 years.