Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma

Ann Oncol. 1996 Dec;7(10):1029-36. doi: 10.1093/oxfordjournals.annonc.a010495.

Abstract

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.

Patients and 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Dose-Response Relationship, Drug
  • Epirubicin / administration & dosage
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Lymphoma, AIDS-Related / drug therapy*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Prednisolone / administration & dosage
  • Recombinant Proteins
  • Vincristine / administration & dosage
  • Zidovudine / administration & dosage*

Substances

  • Anti-HIV Agents
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Epirubicin
  • Zidovudine
  • Vincristine
  • Cyclophosphamide
  • Prednisolone
  • Filgrastim

Supplementary concepts

  • CEOP protocol 2