Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma: evidence for a schedule-dependent effect favoring infusional administration of chemotherapy.
OBJECTIVE
This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features.


METHODS
Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C, most (81%) had received D, and a minority (16%) had received E.


RESULTS
Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10+ to 38+), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38+). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9+ to 24+). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group.


CONCLUSIONS
Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.
Sparano
J A
JA
Department of Medical Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, NY 10467.
Wiernik
P H
PH
Leaf
A
A
Dutcher
J P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged
D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide