De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial.
OBJECTIVE
The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity.


METHODS
Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of ≤ 50%, and 35 (56.5%) had an ejection fraction of > 50% and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension [Corrected]. Primary end point was overall response rate at the end of treatment.


RESULTS
Thirty-eight patients (61.3%; 95% CI, 49.2 to 73.4) achieved disease response (complete response [CR], n = 18; undocumented/unconfirmed CR, n = 6; partial response, n = 14). Two-year progression-free survival for all patients was 49.8% (95% CI, 37.3 to 62.3), and 2-year overall survival was 55.8% (95% CI, 43.3 to 68.4). Thirty-four patients experienced grade ≥ 3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population.


CONCLUSIONS
Our phase II multicenter trial showed that the R-GCVP regimen is an active, reasonably well-tolerated treatment for patients with DLBCL for whom anthracycline-containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease.
Paul A. Fields, Guys and St Thomas' and King's College Hospitals; William Townsend, Nicholas Counsell, Paul Smith, and Nadjet El-Mehidi, Cancer Research UK and University College London Cancer Trials Centre; David C. Linch, University College London Hospital; David Cunnningham, Royal Marsden Hospital, London; Andrew Webb, Royal Sussex Cancer Centre, Brighton; Christopher Pocock, Kent and Canterbury Hospital, Kent; Andrew Jack, St James Hospital, Leeds; Peter W. Johnson, Southampton General Hospital, Southampton; and John Radford, Christie Hospital, Manchester, United Kingdom.
Paul A
PA
Fields
William
W
Townsend
Andrew
A
Webb
Nicholas
N
Counsell
Christopher
C
Pocock
Paul
P
Smith
Andrew
A
Jack
Nadjet
N
El-Mehidi
Peter W
PW
Johnson
John
J
Radford
David C
DC
Linch
David
D
Cunnningham
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015897:Comorbidity; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D000069283:Rituximab; D012720:Severity of Illness Index; D013318:Stroke Volume; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D014750:Vincristine / Q000008:administration & dosage; D000093542:Gemcitabine
D058846:Antibodies, Monoclonal, Murine-Derived; D003841:Deoxycytidine; D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide; D011239:Prednisolone; D000093542:Gemcitabine