title: Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens.
abstract: Pulmonary toxicity may complicate the treatment of non-Hodgkin's lymphoma (NHL). The possible drug-related cause of pulmonary toxicity was investigated retrospectively in 207 NHL patients treated between 1981 and 1988 with three regimens containing cyclophosphamide with and without methotrexate or bleomycin: methotrexate, calcium, leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) (n = 134); methotrexate, calcium, leucovorin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-ACOD) (n = 43); or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 30) chemotherapy. These regimens contained the same drugs and were administered in the same schedule; the regimens differed primarily in the addition of bleomycin or methotrexate. Pulmonary toxicity occurred in 24 of 134 (18%) m-BACOD-treated and in six of 43 (14%) m-ACOD-treated patients (P = 0.65). Chest radiography revealed diffuse pulmonary infiltrates in 16 (67%) and six (100%) of the m-BACOD-treated and m-ACOD-treated patients with pulmonary toxicity, respectively. None of the CHOP-treated patients had pulmonary toxicity. The clinical features of pulmonary toxicity and the amount of chemotherapy administered before it occurred did not differ in patients treated with m-BACOD or m-ACOD, although the toxicity tended to be more severe in the m-BACOD group. Open lung or transbronchial biopsies done in six (38%) of the m-BACOD-treated and three (50%) of the m-ACOD-treated patients with pulmonary infiltrates revealed nonspecific pneumonitis compatible with drug-related toxicity. In summary, these results showed that pulmonary toxicity during m-BACOD and m-ACOD therapy occurred with similar frequency and clinicopathologic features. This suggested that bleomycin was not responsible uniquely for the pulmonary toxicity in m-BACOD-treated patients. That pulmonary toxicity was not observed in patients treated with CHOP suggested that methotrexate may play an important role in the pathogenesis of the pulmonary toxicity.
authors.affiliation: Division of Clinical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: C L
authors.initials: CL
authors.lastname: Shapiro
authors.forename: B Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: J
authors.initials: J
authors.lastname: Godleski
authors.forename: M S
authors.initials: MS
authors.lastname: Jochelson
authors.forename: M A
authors.initials: MA
authors.lastname: Shipp
authors.forename: A T
authors.initials: AT
authors.lastname: Skarin
authors.forename: G P
authors.initials: GP
authors.lastname: Canellos
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D002118:Calcium / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008171:Lung Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011859:Radiography; D012189:Retrospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003520:Cyclophosphamide; D002955:Leucovorin; D002118:Calcium; D011241:Prednisone; D008727:Methotrexate