Dose intensity defined as the amount of
drug used per unit time, expressed as mg/m2/week, was reported to be a significant determinant of antitumor activity of single or combined drugs in
cancer chemotherapy. We formulated a 12 week high dose intensity
chemotherapy (CAMBO-VIP) for the treatment of advanced
non Hodgkin's lymphoma with aggressive histology. The treatment consists of weekly alternate administration of myelosuppressive and non-myelosuppressive agents.
Doxorubicin was administered every other week in combination with either
cyclophosphamide,
etoposide or
ifosfamide. On the weeks in between, non-myelosuppressive
vincristine was given with either
methotrexate with
leucovorin rescue or
bleomycin.
Prednisolone was given for the first and the last 4 weeks.
Dose reduction and
treatment delay were kept minimal for the purpose not lowering dose intensity. As of February 1990, 32 patients (pts), median age 52, entered the study, 29 of whom completed the treatment. There were 3 incomplete cases, in which 2 were due to interruption of the treatment at 5 and 6 weeks, respectively and 1 due to a half dose given because of the old age. CR was obtained in 29 pts (90.6%). Relapse occurred in 3 (10.4%) with the median follow-up of 12 months. Two year disease-free survival (DFS) was estimated to be 76.0% for all the patients and 83.9% for CR patients. Toxicity of CAMBO-VIP was moderate with no chemotherapeutic death. Myelosuppression was severe but of short duration, requiring virtually no
dose reduction.
Treatment delay was 3 days, median, and maximally 28 days. The average actual dose intensity calculated from given amount of drugs and
treatment duration was as high as 90% of the protocol dose intensity. Dose intensity of
CAMBO-VIP protocol is highest, equaling to that of MACOP-B, among representative series of reported
lymphoma protocols. A highly significant correlation was observed between 9
drug relative dose intensity and DFS of the patients treated with each protocol. Significance of dose intensity as an independent prognostic factor, however, should be determined, by a prospective carefully designed stratified randomized studies.