Randomized trials demonstrated the significantly improved survival benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with unresectable advanced gastric cancer (AGC) in comparison with ...best supportive care (BSC). However there is no chemotherapy considered worldwide to be the standard treatment for AGC and there is no consensus as to whether combination or single agent therapy is preferable. Therefore, 2 large Phase III studies JCOG 9912 5-FU vs TS-1 vs CPT + CDDP and TS-1 vs TS-1 + CDDP are now ongoing to establish an acceptable frontline standard for patients with AGC. We need to develop new agents and combination chemotherapy regimens to achieve greater survival benefit in AGC.
There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the ...phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.
In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan.
We retrospectively analyzed ...the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region.
The number of patients enrolled was 38, all of whom were treated after second-line therapy.
The RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days.
At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy.
PDF
