Treatment Of Advanced Gastric Carcinoma Research Articles

Application of intra-arterial infusion chemotherapy in treatment of advanced gastric carcinoma

目的 探讨进展期胃癌术中血管置泵术后靶区化疗的临床疗效.方法 回顾性分析我院453例进展期胃癌切除患者术后的临床资料.按治疗方法的不同将患者分为治疗组和对照组,对其局部复发率、肝转移率及1、3、5年生存率进行对照研究.结果 治疗组局部复发率8.1%,肝脏转移率12.3%,1、3、5年生存率分别为96.8%、77.9%、46.3%;对照组局部复发率22.0%、肝脏转移率26.8%,1、3、5年生存率分别为84.5%、44.6%、21.4%.结论 术中血管置泵术后靶区化疗与传统治疗模式相比,可明显提高术后5年生存率,有效预防局部复发和肝转移。

Docetaxel, Cisplatin, and Fluorouracil; Docetaxel and Cisplatin; and Epirubicin, Cisplatin, and Fluorouracil As Systemic Treatment for Advanced Gastric Carcinoma: A Randomized Phase II Trial of the Swiss Group for Clinical Cancer Research

This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy. Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status <or= 1, and adequate hematologic, hepatic, and renal function randomly received <or= eight 3-weekly cycles of ECF (epirubicin 50 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and fluorouracil [FU] 200 mg/m(2)/d on days 1 to 21), TC (docetaxel initially 85 mg/m(2) on day 1 [later reduced to 75 mg/m(2) as a result of toxicity] and cisplatin 75 mg/m(2) on day 1), or TCF (TC plus FU 300 mg/m(2)/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL). ORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens. Time to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.

Irinotecan Combined with Infusional 5-Fluorouracil and High-Dose Leucovorin for the Treatment of Advanced Gastric Carcinoma as the First-Line Chemotherapy

Background: Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is a need for newer regimens. Methods: Twenty-five chemonaive patients with AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m² over 30 min on day 1 combined with leucovorin 200 mg/m² over 2 h followed by 5-fluorouracil 400 mg/m² as bolus and 600 mg/m² as a 22-hour infusion on day 1 and 2. The treatment was administered every 14th day until progression or intolerable toxicity. Results: Twenty-five patients (17 male, 8 female; 22 patients with PS 0–1 and 3 patients with PS 2), median age 54 (range 25–77), received a total of 230 courses of chemotherapy (median 9; range 1–18). Objective responses were observed in 9 patients (36%), all being partial. Median progression-free survival, 1- and 2-year progression-free survival rates were 8.6 months, 28.4% and 15.3%, respectively. Median overall survival, 1- and 2-year overall survival rates were 11.6 months, 48.0% and 17.8%, respectively. As serious adverse events, grade 3–4 neutropenia was observed in 5 patients (20.0%), grade 3 diarrhea in 4 patients (16.0%). No treatment-related death occurred. Conclusion: FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC.

Mature data on capecitabine (X) + fractionated cisplatin (P) as first-line therapy in patients (pts) with advanced gastric carcinoma (AGC)

4075 Background: Gastric cancer is one of the most common malignancies in Asia with an adjusted mortality rate above 20/100,000 population. 5-FU + fractionated P is a standard treatment for AGC in China. In a Korean study by Kim et al., X + P produced a response rate of 55% in pts with previously untreated AGC. Here we present mature efficacy/safety results in Chinese pts with AGC. Methods: 154 pts of a planned population of 120 pts were enrolled between Jun 2002 and Aug 2004. All had measurable AGC (WHO), Karnofsky performance status ≥60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was permitted. Pts received × 1000 mg/m2 orally bid on days 1–14 + P 20mg/m2/day i.v. on days 1–5, every 3 weeks for 6 cycles. The primary endpoint was time to disease progression (TTP). Results: Baseline characteristics of the 141 evaluable pts (104 men, 37 women) are: median age 54 years (range 23–80), main sites of metastases: lymph nodes 45%, liver 40%, stomach 18%, skin 6%, other 6%, lung 5%, abdomen 4%. The overall response rate was 36%, including 13 complete responses and 38 partial responses. After a median follow-up period of 12 months, the median TTP is 9 months (95% CI, 9–12 months) and the median overall survival is 12 months (95% CI, 12–15 months). Median treatment duration was 6 cycles (range 3–6). The most common treatment-related clinical adverse events (all grades &gt;5%) were: hand-foot syndrome (HFS) 25%, leucopenia 13%, and SGOT abnormality 12%. The most commongrade 3 adverse events were SGPT abnormality 3%, HFS 2%, and anemia 2%. There were no grade 4 adverse events. Most grade 3 adverse events improved or resolved after treatment or interruption except in 1 pt with anemia who withdrew after 2 cycles. Conclusions: X combined with fractionated P is highly active and very well tolerated as first-line treatment for AGC, with comparable results to 5-FU + P. No significant financial relationships to disclose.

Irinotecan combined with infusional 5-fluorouracil and high-dose leucovorin (FOLFORI) for the treatment of advanced gastric carcinoma as the first-line chemotherapy

4164 Background: Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is need for newer regimens. Methods: Twenty-five chemo-naive patients (pts) with stage IV AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m2 over 30 minutes on day (d) 1 combined with leucovorin 200 mg/m2 over 2 h followed by 5-FU 400 mg/m2 bolus and 600 mg/m2 as 22 h infusion on d 1 and 2. The treatment was administered every 14 day until progression or intolerable toxicity. Results: Twenty-five pts (17 male/8 female); median age 54 (range 25–77), 22 pts with PS 0–1 and 3 pts with PS 2), received a total of 230 courses of chemotherapy (median 9; range 1–18). Objective response was observed in 9 pts (36%), all being partial. Median progression-free survival (PFS), 1 and 2 year PFS rates were respectively 9.3 months (mo), 28.4% and 15.3%. Median overall survival (OS), 1 and 2 year OS rates were respectively 12.6 mo, 48.0% and 17.8%. As serious adverse events, grade 3–4 neutropenia was observed in 5 pts (20.0%), grade 3 diarrhea in 4 (16.0%) pts. No treatment-related death occurred. Conclusions: FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC. No significant financial relationships to disclose.

Capecitabine (X) combined with fractionated cisplatin (C) as first-line therapy in Chinese patients (pts) with advanced gastric carcinoma (AGC)

4053 Background: Gastric cancer is one of the most common malignancies in China with a mortality rate of 25.16/100,000 population. Combination of 5-FU and fractionated C is a standard treatment for AGC in China. In a Korean study by Kim et al., X + C produced a response rate of 55% in pts with previously untreated AGC. Therefore, we evaluated the activity and safety of the combination of X and C in Chinese pts with AGC. Methods: 154 pts were enrolled between Jun 2002 and Aug 2004. All had measurable AGC (WHO), Karnofsky performance status ≥60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was permitted. Pts received X 1000mg/m2 orally bid on days 1–14 + C 20mg/m2/day i.v. on days 1–5, every 3 weeks for 6 cycles. Results: 141 pts are evaluable. The remaining 13 pts are not evaluable because they are still receiving treatment. Baseline characteristics: 104 men and 37 women; median age 54 years (range 23–80). Main sites of metastases were: lymph nodes 45%, liver 40%, stomach 18%, skin 6%, lung 5%, abdomen 4%, other 6%. The median treatment duration is currently 6 cycles (range 3–6). Efficacy findings are shown in the table. Median progression-free and overall survival have not yet been reached. The most common treatment-related adverse events (grade 1/2) were: hand-foot syndrome (HFS) 23%, leucopenia 13%, and SGOT abnormality 12%. The most common grade 3 adverse event were SGPT abnormality 3%, HFS 2%, and anemia 2%. There were no grade 4 adverse events. Most grade 3 adverse events improved or resolved after treatment or interruption except in 1 pt with anemia who withdrew after 2 cycles. Conclusions: X combined with fractionated C is highly active and very well tolerated as first-line treatment for AGC, with comparable results to 5-FU + C. No significant financial relationships to disclose.

Noncurative Total Gastrectomy and Oesophagogastrectomy in the Treatment of Advanced Gastric Carcinoma in a Country with High Incidence

The role of extensive resectional surgery, including total gastrectomy for the palliation of advanced gastric cancer is controversial. This study shows operative results with complications and mortality occurring after total gastrectomy in patients with advanced stage gastric carcinoma. The study included 83 (48 males and 35 females, median age was 54.6 ± 11.4 years) patients who underwent palliative total gastrectomy or oesophagogastrectomy (distal oesophagectomy in continuity with total gastrectomy).The reason for nonradical treatment was a too locally advanced disease. There was no case of carcinoma without serosal extension. Only five patients were free of histological lymph node metastases. A total of 72 (86.7%) early postoperative complications, including 17 self-limited wound complications, and 21 pulmonary complications were noted. Dehiscence of the oesophagojejunal anastomosis was noted in 7 patients, 3 of whom subsequently died. A total of 8 (9.6%) patients died in the postoperative period. The mean survival period was 12.8 ±0.8 months for all patients. It was 18.16 ± 2.04 months in stage IIIA patients, 13.37 ± 0.79 months in stage IIIB, and 7.51 ± 0.97 months in stage IV patients. Total gastrectomy is a relatively safe procedure even when performing as a palliative procedure, with acceptable mortality and low lethal complication rate, and should be considered an alternative option in palliative treatment of advanced gastric cancer.

A multi-center, late phase II clinical trial of Genexol® (paclitaxel) and cisplatin for patients with advanced gastric cancer

Because of unsatisfactory treatment results with 5-fluorouracil-based palliative combination chemotherapy for advanced gastric cancer, the evaluation of new effective and well-tolerated regimens is needed. We conducted a multi-center, late phase II trial to evaluate the efficacy and safety of Genexol (a paclitaxel formulation) combined chemotherapy with cisplatin in patients with previously untreated metastatic or unresectable measurable gastric adenocarcinoma. All patients were between 18 and 75 years of age, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and had an adequate baseline major organ function. Genexol 175 mg/m(2) was administered as a 3-h infusion, followed by cisplatin 75 mg/m(2) as an intravenous infusion day 1, once every 3 weeks. Thirty-six patients were enrolled from 7 hospitals between November 2002 and April 2003. Of these, 33 patients were assessable for efficacy and 35 for toxicity. Based on an intent-to-treat analysis, 16 patients (46%) achieved a partial response, 7 (20%) stable disease, and 10 (29%) progressed, giving an overall response rate of 46% (95% CI, 29% to 63%). The median duration of response was 7.1 months (95% CI, 6.3 to 7.9 months), and the median time to progression and overall survival were 4.9 months (95% CI, 3.2 to 6.6 months) and 13.8 months (95% CI, 10.8 to 16.8 months), respectively. The major toxicity was neutropenia, with grade 3/4 intensity in 10 patients (29%). However, no febrile neutropenia occurred, and non-hematologic toxicity was usually mild. Grade 3/4 toxicities included nausea (9% of the patients), vomiting (9%), peripheral neuropathy (9%), alopecia (9%), and myalgia (6%). In conclusion, the combination of Genexol and cisplatin was found to be an active and relatively well-tolerated regimen for the treatment of advanced gastric carcinoma.

Epirubicin, Cisplatin, and Raltitrexed in Patients With Advanced Gastric and Hepatobiliary Carcinoma

The combination of epirubicin, cisplatin, and protracted venous-infusion 5-fluorouracil is the standard treatment of advanced gastric carcinoma in many European countries, and it is also an active regimen in hepatobiliary tumors. Raltitrexed is a specific inhibitor of thymidylate synthase with clinical activity in gastrointestinal malignancies. The aim of the study was to evaluate the clinical activity and toxicity of the combination of epirubicin, cisplatin, and raltitrexed in patients with advanced gastric and hepatobiliary tumors. Twenty consecutive patients with gastric carcinoma, 7 with biliary-tract carcinoma, and 5 patients with hepatocarcinoma were treated with epirubicin (60 mg/m2), cisplatin (60 mg/m2) on day 1, and raltitrexed (1 mg/m2) on days 1 and 8, every 3 weeks. The median age was 63 years (range, 28-76). Eight patients had locally advanced disease and 24 had metastatic tumors. Seven of the 18 evaluable patients (39%) with gastric carcinoma and 2 of the 5 patients with hepatocarcinoma have a partial response; 1 minimal response and 4 stabilization of disease were documented in the 7 patients with biliary-tract carcinoma. The median time to progression of the entire group was 6.8 months, and the median survival was 9.0 months. The toxicity was mild and no toxic death occurred. The combination of epirubicin, cisplatin, and raltitrexed, using this schedule, is tolerable and has clinical activity in gastric and hepatobiliary tumors.

Docetaxel-cisplatin-5FU (TCF) versus docetaxel-cisplatin (TC) versus epirubicin-cisplatin-5FU (ECF) as systemic treatment for advanced gastric carcinoma (AGC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

4020 Background: ECF is currently considered by many as a standard regimen in AGC in Europe. Based on the high efficacy reported with TC and TCF in AGC (Ann. Oncol 11; 301, 2000, ASCO Proc. 18, 245a, 1999), we launched a randomized 3-arm phase II trial to assess which of TC or TCF would be the more promising regimen to compare to ECF in a future phase III trial. Methods: Patients (pts) with AGC, without prior palliative chemotherapy, with bidimentionally measurable disease, PS≤1, normal blood counts, hepatic and renal functions, were randomized to receive up to 8 cycles q3w of TC (docetaxel 85mg/m2, ciplatine 75mg/m2), TCF (like TC + 5-FU continuous infusion (CI) 300mg/m2/d for 2w) or ECF (epirubicin 50mg/m2, cisplatin 60mg/m2, 5-FU CI 200mg/m2/d for 3w). Results: Among 121pts enrolled, 119 were treated and included in the analysis. 5 pts are still on treatment (3 ECF and 2 TCF). Preliminary results are summarized below. A total of 554 treatment cycles are documented up to now. A median of 5, 4.5 and 4 cycles of ECF, TC and TCF were given, respectively. Hematotoxicity was the main toxicity in all 3 arms with grade ≥3 granulopenia in 73%, 76% and 58% of the pts for TC, TCF and ECF, respectively. Febrile neutropenia (FN) occurence in 10 of the first 21 pts enrolled in docetaxel based regimens led to decrease docetaxel from 85 to 75mg/m2 in TC and TCF, resulting in lesser FN occurence. Grade ≥3 non-hematologic toxicity was infrequent (<10% of pts) apart from alopecia (3 arms), nausea (18% in TC and TCF pts) and diarrhea (15% in TCF pts). Conclusions: Despite an increased toxicity, docetaxel based regimens seem to be more efficacious than ECF. In terms of RR and TTP, TCF is the more promising regimen and should be chosen for formal comparison with ECF. This trial is supported in part by Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis

Docetaxel-cisplatin-5FU (TCF) versus docetaxel-cisplatin (TC) versus epirubicin-cisplatin-5FU (ECF) as systemic treatment for advanced gastric carcinoma (AGC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

4020 Background: ECF is currently considered by many as a standard regimen in AGC in Europe. Based on the high efficacy reported with TC and TCF in AGC (Ann. Oncol 11; 301, 2000, ASCO Proc. 18, 245a, 1999), we launched a randomized 3-arm phase II trial to assess which of TC or TCF would be the more promising regimen to compare to ECF in a future phase III trial. Methods: Patients (pts) with AGC, without prior palliative chemotherapy, with bidimentionally measurable disease, PS≤1, normal blood counts, hepatic and renal functions, were randomized to receive up to 8 cycles q3w of TC (docetaxel 85mg/m2, ciplatine 75mg/m2), TCF (like TC + 5-FU continuous infusion (CI) 300mg/m2/d for 2w) or ECF (epirubicin 50mg/m2, cisplatin 60mg/m2, 5-FU CI 200mg/m2/d for 3w). Results: Among 121pts enrolled, 119 were treated and included in the analysis. 5 pts are still on treatment (3 ECF and 2 TCF). Preliminary results are summarized below. A total of 554 treatment cycles are documented up to now. A median of 5, 4.5 and 4 cycles of ECF, TC and TCF were given, respectively. Hematotoxicity was the main toxicity in all 3 arms with grade ≥3 granulopenia in 73%, 76% and 58% of the pts for TC, TCF and ECF, respectively. Febrile neutropenia (FN) occurence in 10 of the first 21 pts enrolled in docetaxel based regimens led to decrease docetaxel from 85 to 75mg/m2 in TC and TCF, resulting in lesser FN occurence. Grade ≥3 non-hematologic toxicity was infrequent (<10% of pts) apart from alopecia (3 arms), nausea (18% in TC and TCF pts) and diarrhea (15% in TCF pts). Conclusions: Despite an increased toxicity, docetaxel based regimens seem to be more efficacious than ECF. In terms of RR and TTP, TCF is the more promising regimen and should be chosen for formal comparison with ECF. This trial is supported in part by Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis

Status of treatment for advanced gastric carcinoma

Gastric cancer is the second most common cause of cancer death worldwide. Advanced gastric cancer is incurable. The most widely investigated single-agent chemotherapy is 5-fluorouracil (5-FU), with partial response rates up to 20%. Pilot phase II studies investigating combinations of 5-FU, anthracyclines, mitomycin, methotrexate, and platinums achieved higher response rates; however, the response rates declined in subsequent larger trials. Furthermore, toxicity was substantially higher in confirmatory trials, emphasizing the need to develop well-tolerated regimens prior to multi-institutional testing. Although phase III studies of combination regimens have not achieved a clear worldwide standard, the regimen of epirubicin, cisplatin, and continuous-infusion 5-FU achieved a survival benefit, possibly through the increased activity of infusional 5-FU combined with cisplatin. The taxanes, irinotecan and oxaliplatin, have recently shown important activity in gastric cancer. Patient accrual to a phase III trial comparing a docetaxel-based combination regimen with the regimen of cisplatin and 5-FU has completed accrual. Whether patients with adenocarcinomas of the proximal stomach and gastroesophageal junction will have the same response rates to these new agents as did patients with classical body and distal gastric cancers is unknown. It is anticipated that the development of these active new agents will ultimately improve survival for patients with advanced gastric cancer.

Pilot Study of Heptaplatin, UFT-E and Leucovorin in Advanced Gastric Carcinoma.

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. 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. 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). 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.

Brief review of advances in the treatment of gastric carcinoma in North America and Europe, 1995-2001.

Gastric carcinoma is widespread in many South American and Asian countries but may be especially deadly in the West, due to a lack of programs for early diagnosis. Advanced gastric carcinoma is incurable, and the median survival time of patients with advanced disease is only 6 to 9 months. We sought to examine investigative trends in the utilization of new agents in the treatment of advanced gastric carcinoma in North America and Europe. Representative published reports of phase II and III clinical trials of therapies for gastric carcinoma by investigators based in North America and Europe from January 1995 through December 2001 were identified by a computerized search of the PubMed literature database. Fluorouracil, cisplatin, leucovorin, methotrexate, doxorubicin, and mitomycin were considered "conventional" agents; all other drugs were considered "new" agents. Of the 42 reports identified by the literature search, 17 were by investigators in North America and 25 were by investigators in Europe. All reports by investigators in North America were phase II trials, compared with 64% of those studies in Europe; the other studies by European investigators were phase III trials (36%). Chemotherapeutic drugs we considered "new" for the purpose of this study were investigated in 64% of all trials in North America and Europe. Eighty-one percent (22/27) of the 27 trials in which new agents were studied were phase II studies. We conclude that new agents are being widely incorporated in the investigation of advanced gastric cancer in North America and Europe. This trend is likely to be continued as more new chemotherapeutic agents are developed for clinical testing.

Laparoscopic surgery of the upper gastrointestinal tract

Laparoscopic surgery of the upper gastrointestinal tract is nowadays associated with little morbidity and mortality. Cardiomyotomy with semifundoplication for management of achalasia and the various forms of fundoplication for treatment of reflux syndrome have proved beneficial and have largely replaced conventional surgery. Independent of the operative approach, it has not yet been established with certainty whether gastroesophageal reflux can best be prevented by 360 degrees fundoplication or semifundoplication. A perforated peptic ulcer can be treated effectively by laparoscopic overstitching of omental patch-plasty, although the superiority of the laparoscopic method has yet to be proved. Benign lesions and early malignancies are currently resected laparoscopically, but the role of laparoscopy in the curative treatment of advanced gastric carcinoma remains to be clarified. Diagnostic laparoscopy is used to avoid unnecessary laparotomy in inoperable cancer and to ascertain whether neoadjuvant therapy is indicated in advanced gastric carcinoma.

Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant chemotherapy.

We report a patient with advanced gastric carcinoma successfully treated with the novel oral fluoropyrimidine anticancer drug TS-1 as neoadjuvant chemotherapy. The patient was a 76-year-old man who had gastric cancer clinically diagnosed as N2T4, invading the pancreas, the duodenum, and the transverse colon. He was treated as an outpatient with TS-1, 120 mg, administered orally every day for 28 days, followed by 14 days' rest, as one course. Two courses resulted in a marked reduction of the tumor without severe toxicity. Subsequently, the patient underwent curative surgery consisting of distal gastrectomy with D2 lymph node dissection. No surgical complications were observed. On microscopic examination, a few tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. Our report is the first to demonstrate the advantages of TS-1 as neoadjuvant chemotherapy for the treatment of advanced gastric carcinoma.

Combination of Bolus 5-Fluorouracil, Folinic Acid and Mitomycin C in Advanced Gastric Cancer: Results of a Phase II Trial

Background: Gastric carcinoma still is a worldwide major cause of cancer death. Although various chemotherapy schedules yielded high response rates, median survival rarely exceeds 8–10 months. Many regimens are inevitably associated with significant toxicity which jeopardizes their value as palliative treatment, especially in patients with reduced performances status. Therefore, we initiated a phase II study for the treatment of advanced gastric carcinoma using a bolus regimen with mitomycin C (MMC), 5-fluorouracil (5-FU) and folinic acid (FA), allowing the enrollment of elderly patients or those with reduced performance status (WHO grade 2). Patients and Methods: Between 1996 and 1998 we recruited a total of 58 patients with advanced gastric cancer to receive bolus MMC 3 mg/m², 5-FU 450 mg/m², and FA 100 mg/m² on days 1–3. Treatment was repeated on day 22. 53 patients met the inclusion criteria: male n = 36, female n =17; median age 65 (range 26–81); mean WHO status 1 (range 0–2). Results: Out of 53 patients 50 were evaluable for response, all 58 patients who received therapy were evaluable for toxicity. Eleven patients (22%) achieved partial remission (95% CI: 11.5 –36.0%), 24 (48%) no change and 15 (30%) were progressive. Median overall survival was 11.5 months, the median time to progression 6.0 months. Out of 290 treatment cycles the worst toxicities observed (WHO 2/3/4) were as follows: anemia 13/3/1, leukopenia 19/1/1, thrombopenia 11/3/0, nausea/emesis 11/2/0, infections 2/1/0, diarrhea 14/2/0, and stomatitis 6/1/1. One patient developed hemolytic-uremic syndrome. Conclusions: The tumor control rate (PR + NC) of 70% was comparable to established chemotherapy regimens, while median overall survival was promising. Toxicity was mild, allowing the treatment especially for elderly patients and on outpatient basis.

Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5-fluorouracil (5-FU), and cisplatin in the treatment of patients with advanced gastric carcinoma. Forty-one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3-hour intravenous (i.v.) infusion on Day 1, 5-FU 750 mg/m2 by 24-hour continuous i.v. infusion on Days 1-5, and cisplatin 20 mg/m2 by 2-hour i.v. infusion on Days 1-5. Twenty-six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity. Twenty-one of the 41 patients (51%; 95% confidence interval [CI], 36.5-65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9-22.5%). Sixty-five percent of the patients with measurable disease (17 of 26; 95% CI, 58-92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1-52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4-90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred. Paclitaxel, 5-FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting.

Paclitaxel, 5‐fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

Paclitaxel, 5‐fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

A phase II study of 5-fluorouracil, leucovorin, and interferon-? in the treatment of patients with metastatic or recurrent gastric carcinoma

Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.