Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial

• DOI: 10.1016/j.ejca.2015.02.009
• Publication Date: 2015-03-25T18:03:13Z
• Authors: Kazuhiro Nishikawa; Kazumasa Fujitani; Hitoshi Inagaki; Yusuke Akamaru; Shinya Tokunaga; Masakazu Takagi; Shigeyuki Tamura; Naotoshi Sugimoto; Tadashi Shigematsu; Takaki Yoshikawa; Tohru Ishiguro; Masato Nakamura; Satoshi Morita; Yumi Miyashita; Akira Tsuburaya; Junichi Sakamoto; Toshimasa Tsujinaka
• Keywords: Adult; Male; Cancer Research; Second-line; Adenocarcinoma; Irinotecan; Combination chemotherapy; 03 medical and health sciences; Phase III; 0302 clinical medicine; Stomach Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Humans; Treatment Failure; Aged; Tegafur; Aged, 80 and over; S-1; Middle Aged; 3. Good health; Drug Combinations; Oxonic Acid; Oncology; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Disease Progression; Camptothecin; Female; Cisplatin; Gastric cancer; Fluoropyrimidine

The optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy.AGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m(2); CDDP, 30 mg/m(2), q2w) or CPT-11 (150 mg/m(2), q2w).Sixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8-17.6) and 12.7 (95% CI: 10.3-17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596-1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4-5.9] versus 4.1 [95% CI: 3.3-4.9]months) and response rate (16.9% [95% CI: 8.8-28.3] versus 15.4% [95% CI: 7.6-26.5]). The incidences of grade 3-4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019).No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.