Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma.
BACKGROUND
A phase I/II trial determined the maximum tolerated dose (MTD) of CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concurrent filgrastim and antiretroviral therapy.


METHODS
Fourteen AIDS-NHL patients, chemotherapy naïve and ECOG performance status < 2 received filgrastim 1.0 microgram/kg s.c. daily for 3-7 days to assess neutrophil response, followed by CEOP with filgrastim support 10 micrograms/kg s.c. daily, day 2-14, continued if the absolute neutrophil count (ANC) < 1.2 x 10(9)/l. Two CEOP dose cohorts were used: cohort 1 (5 patients) - cyclophosphamide (C) 500 mg/m2, epirubicin (E) 37.5 mg/m2, vincristine (O) 2 mg and prednisolone (P) 75 mg/m2 daily on days 1-5; cohort 2 (9 patients) - C 750 mg/m2, E 50 mg/m2, same doses of O and P. Antiretroviral therapy was maintained (zidovudine-10, ddI-3, both-1).


RESULTS
In cohort 1, 4/5 patients received at least 3 courses of CEOP with one complete response after five cycles and four progressions. Four have died (3-21 months after entry) with 1 alive at 40 months. Dose limiting toxicity (DLT - grade IV febrile neutropenia in cycle 1) occurred in 1 patient. In cohort 2, 5/9 completed > or = 5 cycles with 6 complete responses, 1 partial response and 2 progressions, 6 deaths and 3 alive at > 33 months. DLT (evaluable in 8 patients) occurred in two patients. Median survival for both cohorts was 17 months. Mean relative dose intensity was > 85%.


CONCLUSIONS
The dosages of CEOP in cohort 1 defined the MTD however, the cohort 2 doses with filgrastim and antiretroviral therapy gave an encouraging response, acceptable toxicities and merit further study.
Newell
M
M
National Center in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Goldstein
D
D
Milliken
S
S
Lewis
C
C
Hoy
J
J
Thomson
B
B
Cooper
D
D
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D011994:Recombinant Proteins; D014750:Vincristine / Q000008:administration & dosage; D015215:Zidovudine / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D015215:Zidovudine; D014750:Vincristine; D003520:Cyclophosphamide; D011239:Prednisolone; D000069585:Filgrastim