CLINICAL TRIAL REPORT Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL John L. Reagan • Alan Rosmarin • James N. Butera • Ahmed Nadeem • Fred J. Schiffman • William M. Sikov • Eric Winer • Anthony E. Mega Received: 28 February 2011 / Accepted: 29 June 2011 / Published online: 15 July 2011 Ó Springer-Verlag 2011 Abstract Purpose Gemcitabine induces a 20% response as single- agent therapy in patients with relapsed or refractory NHL. We report phase I findings of gemcitabine in combination with standard CHOP chemotherapy with G-CSF sup- port for intermediate grade NHL. The protocol was mod- ified during enrollment to include rituximab in CD 20? lymphomas. Methods Patients received CHOP plus gemcitabine at 500 mg/m 2 (Cohort 1) or 750 mg/m 2 (Cohort 2) on days 1 and 4 of each 21-day cycle. Accrual was suspended once each cohort was filled. Dose escalation occurred after all patients in the cohort were determined to not have a dose- limiting toxicity. Results Between April 2002 and May 2004, 10 patients were enrolled and completed the study treatment (6 in Cohort 1, 4 in Cohort 2). In Cohort 1, grade 3 toxicities included neutropenia, anemia, neuropathy, and constipa- tion. Grade 4 toxicities were febrile neutropenia and thrombocytopenia. In Cohort 2, grade 3 toxicities included neutropenia, thrombocytopenia, mucositis, anemia, and intestinal obstruction. Grade 4 toxicities included febrile neutropenia, neutropenia, and thrombocytopenia. One patient developed MDS 36 months after chemotherapy. Three of four patients in Cohort 2 developed dose-limiting toxicities (mucositis and thrombocytopenia) requiring dose reduction in gemcitabine after cycle 1. Overall, the survival rate at 2.5 years was 71%. Conclusions This Phase I trial concludes that gemcita- bine 500 mg/m 2 on days 1 and 4 of each 21-day cycle is the maximum tolerated dose when combined with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. Keywords Non-Hodgkins lymphoma Á Lymphoma Á Gemcitabine Á NHL Introduction Yearly, an estimated 65,540 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed, while 20,210 men and women will die of NHL [1]. Multidrug combination che- motherapy regimens have improved the outlook of patients with NHL with the most historically common regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) administered every 3 weeks [2]. Numerous studies sought to find a more curative regimen than CHOP alone. Since rapidity and completeness of response appear to correlate with durability of remission [3], second and third generation combination regimens were established as more intensive alternatives to CHOP chemotherapy in patients with aggressive NHL. However, despite more intensive treatment, no combination regimen was shown to be more beneficial than CHOP [4–10] while some of the second and third generation regimens actually possessed greater toxicities [4, 5]. Recently, new combination regimens have been used with promising results. Trials utilizing ACVBP [11, 12] as well as NHL-15 [13] have shown improved response over CHOP alone in aggressive NHL. These trials did not take into account the addition of rituximab to CHOP, which has been documented to improve response and survival without J. L. Reagan (&) Á A. Rosmarin Á J. N. Butera Á A. Nadeem Á F. J. Schiffman Á W. M. Sikov Á E. Winer Á A. E. Mega Department of Hematology/Oncology, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA e-mail: jreagan@lifespan.org 123 Cancer Chemother Pharmacol (2011) 68:1075–1080 DOI 10.1007/s00280-011-1702-0