Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer.
One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m2) or cisplatin (60 mg/m2) was given over 1 hour with 5-FU (1 gm/m2) on days 1~5 every 4 weeks.
At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths.
Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.
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Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer.
Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m2/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m2/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks.
Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state.
This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.
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To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.
Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m2 iv on day 1, heptaplatin 400 mg/m2 iv on day 2 and 5-fluorouracil 800 mg/m2 on day 2~4 were administered and the regimen was repeated every 3 weeks.
The median age of the patients was 60 years (range: 32~74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26~8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48~6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26~17.44). A median of 3 cycles (range: 1~7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life-threatening complication of pneumonia.
The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.
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