A Phase II Study with Cyclophosphamide, Vincristine, Liposomal Doxorubicin (Myocet™), and Prednisone Plus Rituximab, Administered in a Two Weeks Regimen (R-COMP-14) as Primary Treatment for NHL: Efficacy and Safety Interim Analysis.

BACKGROUND: R-CHOP every 21 days is the standard front line therapy for CD20+ aggressive B-cell non-Hodgkin lymphoma (DLBCL). Intensification of R-CHOP from 21 to 14 days courses with growth factors prophylaxis has shown better outcome and acceptable tolerability. Liposomal doxorubicin (Myocet™) has demonstrated significant less cardiotoxicity than standard doxorubicin. The aim of the study is to assess the efficacy and safety of dose dense R-CHOP regimen modified with Myocet™ (R-COMP-14) in newly diagnosed aggressive DLBCL. Pegfilgrastim was administered to provide prophylactic neutropenia support.

METHODS: Between Dec 04 and Aug 07, 47 patients (pats.) were included in the trial. Interim analysis results of the first 36 evaluable pats. completing the study are reported. CD20+, newly diagnosed DLBC non-Hodgkin lymphoma pats. were treated with Rituximab (375 mg/m2), Cyclophosphamide (750 mg/m2), Vincristine (1.4 mg/m2; max. 2 mg), Myocet™ (50 mg/m2) on day 1 and oral Prednisone (100 mg) on days 1 to 5. Pegfilgrastim was administered on day 2 at standard dose. A maximum of 8 cycles, administered every 14 days, were given. Response was assessed at cycle 3, and patients with complete or partial response received 5 additional courses. Pats. characteristics at baseline were: Median age of 55 years (range 27–65); Ann Arbor stage I-II (IPI >1) 38.2%, III 29.4%, IV 32.4%; Extranodal involvement was present in 54.3% pats. ECOG 0: 44.4%, ECOG 1: 41.7%; ECOG 2: 13.9%. Median basal LVEF was 65% (range 40–80).

RESULTS: The median relative intensity per week of the chemotherapy regimen was 93.7%. A total of 228 cycles were given, 11 (4.8%) were delayed and 9 cycles (3.9%) were dose reduced mainly due to haematological toxicity. Twenty-four patients (66.7%) completed 8 cycles of treatment. Patients withdrew the study because of investigator or patient decision (7 pats.), unrelated adverse events (2 pats.), haematological or gastrointestinal toxicity (2 pats.) and progression disease (1 pat.). Tolerability: Haematological Grade 3–4 toxicity was: Febrile neutropenia in 2.7% cycles; neutropenia in 3.0% cycles; anaemia in 0.8% cycles and thrombocytopenia in 0.4% cycles. Non-haematological G 3–4 toxicities were gastrointestinal, emesis, nausea/vomiting, hepatic, and asthenia observed in 1.1% of the cycles each; G 3 neurotoxicity and infection were observed in one cycle each. No additional G 3–4 toxicities were recorded. Median LVEF at final visit was 63% (range 52–76). No cardiac episode was observed. Efficacy: Overall response rate was 83.4% (95% CI: 67.2%–93.6%). 24 pts. (66.7%) achieved a complete response (CR/uCR) and 6 pts. (16.7%) a partial response (PR); 2 pats (5.6%) had stable disease and 4 (11.1%) progression disease.

CONCLUSIONS: Dose dense R-CHOP modified with liposomal doxorubicin (R-COMP-14) and supported with prophylactic pegfilgrastim is an effective treatment for DLBC non Hodgkin lymphoma, that shows good tolerability profile and no cardiac events. The good efficacy and safety results justifie continuation until the foreseen 75 patients.