Docetaxel/cisplatin followed by FOLFIRI versus the reverse sequence in metastatic gastric cancer.
BACKGROUND
Both docetaxel-based and irinotecan-based chemotherapy has been demonstrated as active combination regimen in either first-line or second-line setting for metastatic gastric cancer. The purpose of this trial was to evaluate the two active regimens, docetaxel/cisplatin and FOLFIRI, as first- and second-line chemotherapy and to compare the sequence of the two regimens in terms of efficacy and tolerability.


METHODS
Eligible patients were randomized to receive one of the two treatment arms: Arm A-DP (docetaxel 75 mg/m(2) D1, cisplatin 75 mg/m(2) D1 repeated every 3 weeks) until progression or unacceptable toxicity as the first-line treatment which was followed by FOLFIRI (irinotecan 150 mg/m(2) D1, leucovorin 100 mg/m(2) D1, 5-fluorouracil 3,000 mg/m(2) D1-2 for 48 h every 2 weeks) upon disease progression as second-line chemotherapy; Arm B-FOLFIRI as the first-line treatment until disease progression or unacceptable toxicity then followed by DP as the second-line treatment upon documented disease progression.


RESULTS
Between April 2005 and Aug 2008, 58 patients were enrolled (Arm A, n = 28; Arm B, n = 30). Median follow-up was 38.2 months. The overall response rate (ORR) of the first-line chemotherapy was 25.0% with DP (Arm A1) and 13.3 with FOLFIRI (Arm B1) (P = 0.322). The tumor control rate (TCR) of first-line chemotherapy was 82.1% with DP and 66.7% with FOLFIRI (P = 0.209). The median first progression-free survival (1st PFS) was 4.3 months with DP and 3.4 months with FOLFIRI (P = 0.547). The overall response rate of second-line chemotherapy was 20.0% with FOLFIRI (Arm A2) and 27.2% with DP (Arm B2) (P = 0.296). The tumor control rate of second-line chemotherapy was 46.7% with FOLFIRI and 50.0% with DP. The median second progression-free survival (2nd PFS) was 8.1 months with Arm A and 6.7 months with Arm B (P = 0.865). The median overall survival was 12.5 months (95% CI 8.17-16.83) in Arm A and 13.4 months (95% CI 9.99-16.81) in Arm B (P = 0.674). In safety profile, the incidence of neutropenic fever was comparable among the 4 arms ranging from 0 to 3.9%.


CONCLUSIONS
The ORR, TCR of Arm A (DP → FOLFIRI) were not different from those of Arm B (FOLFIRI → DP). There was no statistically significant difference in 1st PFS, 2nd PFS, and OS of both arms. Although the trial was terminated early due to poor patient accrual, we found that both DP and FOLFIRI regimens were tolerable with comparable efficacies regardless of the sequence administered.
Kim
Jung A
JA
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Kangnam-ku, Seoul 135-710, Korea.
Lee
Jeeyun
J
Han
Boram
B
Park
Se Hoon
SH
Park
Joon Oh
JO
Park
Young Suk
YS
Lim
Ho Yeong
HY
Kang
Won Ki
WK
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin