Open AccessCombination of CCNU and DTIC Chemotherapy for Treatment of Resistant Lymphoma in Dogs
Author(s) -
Flory A.B.,
Rassnick K.M.,
AlSarraf R.,
Bailey D.B.,
Balkman C.E.,
Kiselow M.A.,
Autio K.
Publication year - 2008
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/j.1939-1676.2007.0005.x
Subject(s) - medicine , lomustine , vincristine , chemotherapy , dacarbazine , gastroenterology , lymphoma , canine lymphoma , prednisone , cyclophosphamide , combination chemotherapy , surgery , pharmacology
Background: Pleotropic‐glycoprotein (P‐gp)–mediated resistance is the usual cause of relapse in dogs with lymphoma. 1‐(2‐chloroethyl)3‐cyclohexyl‐1‐nitrosurea (CCNU) and 5‐(3,3‐dimethyl‐1‐triazeno)‐imidazole‐4‐carboxamide (DTIC) are alkylating agents that are not affected by P‐gp and lack cross‐resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity. Hypothesis: A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy. Animals: Fifty‐seven dogs with lymphoma that were resistant to treatment with standard chemotherapy ( l ‐CHOP; l ‐asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone). Methods: Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5‐h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks. Results: Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m 2 PO combined with DTIC at 600 mg/m 2 IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The median l ‐CHOP CR duration of the dogs that did not respond to CCNU‐DTIC was significantly longer than that of the dogs that did achieve remission with CCNU‐DTIC (225 days versus 92 days, P = .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/μL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs. Conclusions and Clinical Importance: A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.