Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG).
BACKGROUND
Gemcitabine has been shown to have activity as a single agent in lymphoma and, when combined with cisplatin, is effective therapy for a number of solid tumors. The authors wished to determine the response rate and toxicity of gemcitabine, dexamethasone, and cisplatin for recurrent or refractory non-Hodgkin lymphoma (NHL).


METHODS
Patients with recurrent or refractory diffuse large B-cell NHL or variants (REAL classification), measurable disease, and one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on Days 1 and 8, dexamethasone 40 mg orally on Days 1-4, and cisplatin 75 mg/m(2) i.v. on Day 1 (GDP), every 21 days as an outpatient. The primary end point was a response after two cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles.


RESULTS
Fifty-one eligible patients were evaluable for toxicity and response. The median age of the patients was 57 years (range, 18-84 years) and most had diffuse large-cell lymphoma. After 2 cycles, there were 8 complete responses (CR; 16%) and 17 partial responses (PR; 33%). There was an overall response rate (RR) of 49% (95% confidence interval = 37-63%). The RR afer completion of all protocol chemotherapy (including those who received > 2 cycles of GDP) was 53% (11 CR, 16 PR). Grade 3 and 4 neutropenia occurred in 33% and 39% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 24% and 4% of patients, respectively. Seven patients (14%) experienced febrile neutropenia. Of the 35 patients < 66 years, 22 (63%) proceeded to SCT.


CONCLUSIONS
GDP is an active regimen in B-cell NHL and can be administered with acceptable toxicity to outpatients. A Phase III trial comparing GDP with standard cisplatin-based chemotherapy is now ongoing through the National Cancer Institute of Canada Clinical Trials Group.
Crump
Michael
M
National Cancer Institute of Canada-Clinical Trials Group, Kingston, Ontario, Canada. michael.crump@uhn.on.ca
Baetz
Tara
T
Couban
Stephen
S
Belch
Andrew
A
Marcellus
Deborah
D
Howson-Jan
Kang
K
Imrie
Kevin
K
Myers
Robert
R
Adams
Grenfell
G
Ding
Keyue
K
Paul
Nancy
N
Shepherd
Lois
L
Iglesias
Jose
J
Meyer
Ralph
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D003841:Deoxycytidine; D003907:Dexamethasone; D002945:Cisplatin