Randomized, Multicenter, Phase III Trial of Heptaplatin 1-hour Infusion and 5-Fluorouracil Combination Chemotherapy Comparing with Cisplatin and 5-Fluorouracil Combination Chemotherapy in Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Combination Chemotherapy of Heptaplatin, Paclitaxel and 5-Fluorouracil in Patients with Advanced Gastric Cancer: a Pilot Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. MATERIALS AND METHODS: Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m(2) iv on day 1, heptaplatin 400 mg/m(2) iv on day 2 and 5-fluorouracil 800 mg/m(2) on day 2~4 were administered and the regimen was repeated every 3 weeks. RESULTS: 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. CONCLUSION: 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.

Combination Chemotherapy with 5-Fluorouracil and Heptaplatin as First-line Treatment in Patients with Advanced Gastric Cancer

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

5-Fluorouracil, heptaplatin and UFT combination chemotherapy for advanced or recurrent gastric cancer / 대한내과학회지

BACKGROUND: This study was performed in patients with advanced or recurrent gastric cancer to evaluate the efficacy and feasibility of combination chemotherapy with 5-fluorouracil, heptaplatin, and UFT. METHODS: Total 20 patients with advanced or recurrent gastric cancer were enrolled from April 1, 2000 to December 31, 2001 and analyzed for response, toxicity, and survival. The regimen consisted of heptaplatin 400 mg/m2 (day 1), 5-flurouracil 1,000 mg/m2/day (day 1 to 5, continuous infusion) and 5-FU 225 mg/m2/day (day 6 to 12, continuous infusion) or UFT 400 mg/d (day 6 to 22). The treatment was repeated by 28 days. RESULTS: 17 patients could be evaluated. The overall response rate was 47.1% (2 complete responses and 6 partial responses), and the median duration of response was 6.2 months (95% CI: range, 1.0~12.4 months). Median survival of the 20 patients was 11.7 months (95% CI: range, 4.2~19.8 months). Grade 4 hematologic toxicity with sepsis occurred in 1 cycle. CONCLUSION: Based on these results, this combination chemotherapy seems to be useful for advanced or recurrent gastric cancer.

Phase I and Pharmacokinetic Study of Intraoperative Intraperitoneal Heptaplatin in Patients with Surgically Resected Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin, a new platinum analog, has favorable toxicity profiles and antitumor activity, comparable to those of cisplatin, in the treatment of gastric cancer. This study was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of heptaplatin administered by an intraperitoneal route in patients with resected advanced gastric cancer. MATERIALS AND METHODS: Seventeen patients with resected advanced gastric cancer were entered onto the study. After completion of a curative resection and an astomosis, heptaplatin was administered intraperiton eally in one liter of 5% dextrose solution. The starting heptaplatin dose was 400 mg/m2 of the body surface area, and was escalated in 200 mg/m2 increments, to cohorts of three patients. A pharmacokinetic analysis was carried out to determine the total and ultrafiltratable platinum concentrations in the plasma, peritoneal fluid, and urine. RESULTS: Patients were unable to tolerate a 1, 000 mg/m2 dose level, and at 800 mg/m2, reVersible Grade III toxic ities, including elevated creatinine, proteinuria, hypon- atremia, abdominal pain, and intraabdominal bleeding were noted. No significant toxicity was noted up to a 600 mg/m2 dose level. The ratio of the peak peritoneal to peak plasma drug concentrations were 19.4, 16.6 and 22.8 at doses of 400 mg/m2, 600 mg/m2 and 800 mg/m2, respectively. The pharmacological advantage, expressed as the peritoneal to plasma AUC ratio ranged from 4.3 to 7.0. CONCLUSION: Heptaplatin can be delivered by an intra peritoneal route, with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The MTD of intraperitoneal heptaplatin was 800 mg/m2. The major DLTs were nephrotoxicity and intraabdominal bleeding. The recommended starting dose for a subsequent study would be 600 mg/m2.

Pilot Study of Heptaplatin, UFT-E and Leucovorin in Advanced Gastric Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (SKI-2053R, Sunpla ), a new platinum analogue which has a better toxicity profile than cisplatin, has been used with 5-fluorouracil (5-FU) continuous infusion for the treatment of advanced gastric carcinoma. However, continuous 5-FU infusion had a inconvenience to administration. The aim of this study was to evaluate the efficacy and toxicity of heptaplatin, UFT-E and leucovorin combination chemotherapy in advanced gastric cancer. MATERIALS AND METHODS: A total of 22 patients was enrolled in this study at Kyung Hee University and Korea University from September 1999 to May 2001. Heptaplatin 400 mg/m2 was given as intravenous infusion for 1 hour at day 1. Oral UFT-E 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. RESULTS: The 22 enrolled patients received 81 courses of chemotherapy and the median number of course per patient was three with a range of one to six. Five of 21 patients achieved partial responses (23.8%; 95% confidence interval, 5.6% to 42%) without complete response. Out of the 5 responding patients, three had unresectable perigastric lymph-nodes, one patient had a ovarian metastasis, and one patient had a peritoneal metastasis respectively. Main toxicities were neutropenia and nausea/vomiting. Grade 3 and 4 neutropenia were observed in 4 patients (18%) and grade 3 nausea/vomiting were observed in 5 patients (22.7%). The median time to progression was 4 months (range, 0.5 to 13 months), and median survival duration was 7.5 months (range, 2.0 to 14 months). Median response duration was 5.0 months (range, 1.5 to 10 months). CONCLUSION: A combination chemotherapy of heptaplatin, UFT-E and leucovorin has a comparable efficacy with those of previously reported heptaplatin and intravenous regimen of 5-FU and controllable toxicity in advanced gastric carcinoma. Further study with large patient population is warranted to determine the usefulness of this regimen.

Papillary Serous Carcinoma in Rectum-a Case of Complete Remission of Bulky Pelvic Disease after Platinum-paclitaxel Combination Chemotherapy

Papillary serous carcinoma of the peritoneum (PSCP) is a primary tumor of peritoneal lining (mesothelioma) of the abdomen and is histologically difficult to differentiate from papillary serous carcinoma of the ovary. It is very rare tumor that involves the surface of the pelvic and/or abdominal peritoneum. Most patients with this tumor have been treated with optimally surgical cytoreduction and postoperative chemotherapy. However, long term survival has not been achieved in many studies. In recent years, platinum-paclitaxel combination therapy was reported as a effective initial therapy for recurrent PSCP. We have experienced one case of recurrent PSCP which was successfully treated with heptaplatin and paclitaxel. We report the toxicity and long term result of the patient.