Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity.

BACKGROUND: Gemcitabine is an effective treatment for recurrent Hodgkin disease (HD), with relatively minimal associated toxicity. The authors conducted a trial substituting this drug for dacarbazine in the standard regimen to form ABVG (doxorubicin, bleomycin, vinblastine, gemcitabine) for patients with newly diagnosed, high-risk HD.
METHODS: Twelve patients (median age, 34 years) with advanced-stage de novo HD were enrolled. Standard doses of doxorubicin, bleomycin, and vinblastine were given for six cycles. Cohorts of three patients were enrolled and the dose of gemcitabine was escalated to identify the maximally tolerated dose in this combination.
RESULTS: The maximally tolerated dose of gemcitabine was determined to be 800 mg/m(2) in this combination. Five patients developed clinically significant pulmonary toxicity. Three required hospitalization during the final two cycles of treatment. Pneumonitis could not be predicted with serial diffusion capacity for carbon monoxide (DECO) evaluations, and reversed after discontinuation of bleomycin in three patients and steroid therapy in two patients. All 12 patients are alive to date, and 4 patients have experienced disease progression.
CONCLUSIONS: The bleomycin/gemcitabine combination should not be pursued for de novo HD due to significant pulmonary toxicity. Copyright 2003 American Cancer Society.