PMID- 12691141 OWN - NLM STAT- MEDLINE DCOM- 20031002 LR - 20190116 IS - 1042-8194 (Print) IS - 1026-8022 (Linking) VI - 44 IP - 1 DP - 2003 Jan TI - Treatment of the chronic phase of chronic myeloid leukemia with an intermittent schedule of recombinant interferon alfa-2b and cytarabine: results from CALGB study 9013. PG - 39-48 AB - Despite nine studies reporting the results achieved when treating patients with chronic myeloid leukemia (CML) with interferon (rIFNalpha) and cytarabine (araC), the optimal doses and schedule for this combination remain to be determined. Results of imatinib mesylate (STI-571) in chronic phase CML are preliminary, thus, trials of rIFNalpha-2b/araC in CML are of continued interest. We report the results of CALGB study 9013, providing a 10-year follow-up on 88 evaluable previously untreated patients. Cycles of therapy with rIFNalpha-2b and araC sufficient to cause a decline in either the white blood cell (WBC) count to < 2000/microl or platelets to < 50,000/microl were given. The starting dose of rIFNalpha-2b was 5 million units (mu)/m2/day subcutaneously (s.c.) and of araC 10 mg/m2 twice daily s.c. Treatment was discontinued when cytopenia occurred and was restarted when both the WBC and platelet counts had recovered. Bone marrow was obtained regularly for morphologic, cytogenetic and molecular studies. Medians at entry included age 48 years, WBC = 89,900/microl and platelets = 345,000/microl. The performance status was 0 or 1 in 88%; splenomegaly was present in 46%. Fifty five (63%) patients had a complete hematologic response and 10 (11%) had a partial hematologic response for an overall response rate of 74%. Median time to best response was 5.3 months. Median survival for all patients from study entry was 81 months, the 5-year survival probability was 65%. When 28 patients were censored at the time of bone marrow transplantation the median survival was 82 months. Grade 3 anorexia, nausea, vomiting and diarrhea developed in 15, 27, 13 and 7%, respectively. Mild to moderate elevations of transaminases occurred in 42%, and were severe in 5%. Sixty-three patients had adequate follow-up cytogenetic studies: 10 had a complete cytogenetic response (CCyR), 23 partial (PCyR, 50-99% normal cells), 20 minor and 10 no response (CALGB criteria). Thus, the CCyR plus PCyR rate among these 63 patients was 52%. Assuming the 25 patients with no cytogenetic follow-up as non-responders, 38% of the 88 patients had at least a PCyR. The median time to CCyR or PCyR was 5.6 months. The median time to best response in these 33 patients was 10.0 months, and median duration of cytogenetic response was 28 months. Cytogenetic responders had significantly longer survival than non-responders (p = 0.01) using a landmark analysis at 18 months. This intermittent schedule of rIFNalpha-2b/ara-C has a high response rate in patients with CML with acceptable toxicity. FAU - Silver, Richard T AU - Silver RT AD - Weill Medical College of Cornell University, Division of Hematology Oncology, 525 E. 68th St Box 581, New York, NY 10021, USA. rtsilve@med.cornell.edu FAU - Peterson, Bercedis L AU - Peterson BL FAU - Szatrowski, Ted P AU - Szatrowski TP FAU - Powell, Bayard L AU - Powell BL FAU - Stock, Wendy AU - Stock W FAU - Carroll, Andrew J AU - Carroll AJ FAU - Bloomfield, Clara D AU - Bloomfield CD FAU - Schiffer, Charles A AU - Schiffer CA FAU - Larson, Richard A AU - Larson RA LA - eng GR - 16058/PHS HHS/United States GR - 77658/PHS HHS/United States GR - CA02599/CA/NCI NIH HHS/United States GR - CA03927/CA/NCI NIH HHS/United States GR - CA04326/CA/NCI NIH HHS/United States GR - CA04457/CA/NCI NIH HHS/United States GR - CA07968/CA/NCI NIH HHS/United States GR - CA08025/CA/NCI NIH HHS/United States GR - CA11028/CA/NCI NIH HHS/United States GR - CA11789/CA/NCI NIH HHS/United States GR - CA12046/CA/NCI NIH HHS/United States GR - CA21060/CA/NCI NIH HHS/United States GR - CA31809/CA/NCI NIH HHS/United States GR - CA31946/CA/NCI NIH HHS/United States GR - CA31983/CA/NCI NIH HHS/United States GR - CA32291/CA/NCI NIH HHS/United States GR - CA33601/CA/NCI NIH HHS/United States GR - CA35091/CA/NCI NIH HHS/United States GR - CA35279/CA/NCI NIH HHS/United States GR - CA41287/CA/NCI NIH HHS/United States GR - CA47555/CA/NCI NIH HHS/United States GR - CA47559/CA/NCI NIH HHS/United States GR - CA47577/CA/NCI NIH HHS/United States GR - CA47642/CA/NCI NIH HHS/United States GR - CA77440/CA/NCI NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (Recombinant Proteins) RN - 04079A1RDZ (Cytarabine) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use/toxicity MH - Blotting, Southern MH - Central Nervous System Diseases/chemically induced MH - Cytarabine/*administration & dosage MH - Drug Administration Schedule MH - Female MH - Follow-Up Studies MH - Fusion Proteins, bcr-abl/analysis MH - Humans MH - Interferon alpha-2 MH - Interferon-alpha/*administration & dosage MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications/*drug therapy/mortality MH - Male MH - Middle Aged MH - Recombinant Proteins MH - Survival Analysis EDAT- 2003/04/15 05:00 MHDA- 2003/10/03 05:00 CRDT- 2003/04/15 05:00 PHST- 2003/04/15 05:00 [pubmed] PHST- 2003/10/03 05:00 [medline] PHST- 2003/04/15 05:00 [entrez] AID - 10.1080/1042819021000040260 [doi] PST - ppublish SO - Leuk Lymphoma. 2003 Jan;44(1):39-48. doi: 10.1080/1042819021000040260.