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.
Friedberg
Jonathan W
JW
James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, PO Box 704, Rochester, NY 14642, USA. Jonathan_Friedberg@urmc.rochester.edu
Neuberg
Donna
D
Kim
Helen
H
Miyata
Sarah
S
McCauley
Mary
M
Fisher
David C
DC
Takvorian
Tak
T
Canellos
George P
GP
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
D003841:Deoxycytidine; D001761:Bleomycin; D014747:Vinblastine; D004317:Doxorubicin