Second-line chemotherapy in gastric cancer following S-1 with CPT-11 chemotherapy performed as clinical trial

We previously conducted a phase I/II study of irinotecan (CPT-11) combined with S-1 as first-line chemotherapy for metastatic advanced gastric cancer. In the present study,second-line chemotherapy was given to 32 of 44 patients whose disease became refractory to this first-line treatment. Overall survival time of the patients given second-line chemotherapy was significantly longer than that of patients not given such therapy (444 days vs. 230 days, p = 0.013). The response rate to second-line chemotherapy was 13% (4/32). Survival time of patients who responded to second-line chemotherapy was significantly longer than that of non-responders. Second-line chemotherapy may produce a better clinical response in patients who have progressive disease during first-line chemotherapy. Overall survival time and time to progression after second-line chemotherapy did not significantly differ between patients who received second-line chemotherapy regimens including S-1 and those who received regimens not including S-1.     

Efficacy of low-dose CDDP and CPT-11 for patients with intestinal type of gastric adenocarcinoma

BACKGROUND: Preclinical studies have shown that irinotecan (CPT-11) and cisplatin (CDDP) can act synergistically. Several chemotherapy regimens combining CPT-11 and CDDP for advanced gastric cancer have been reported to demonstrate high response rates and high incidence of severe toxicity. PURPOSE: We conducted a combination chemotherapy regimen of low-dose CDDP and CPT-11 to prolong the time to progression with less toxicity. PATIENTS AND METHODS: Seven patients with histologically-confirmed intestinal type of gastric adenocarcinoma were enrolled in this study. All patients were male, and their age at diagnosis ranged from 52 to 76 with a mean age of 64.8. Six patients received combination chemotherapy with CPT-11 and CDDP after the gastrectomy (stage I b: 1, II : 3, III b: 1, IV: 1). Only chemotherapy was administered in one patient because of a far advanced primary lesion and metastatic tumors. Low-dose CDDP (20 mg/body) and CPT-11 (65 mg/m(2)) were administered intravenously once every two weeks. RESULTS: The overall response rate was 43% including 1 complete response and 2 partial responses. One patient had grade 3 myelosuppression. Other adverse reactions were mild. CONCLUSION: The combination of low-dose CDDP and CPT-11 has mild therapeutic toxicities and may achieve a prolonged median survival time in patients with intestinal- type gastric adenocarcinoma.     

Latest progress on chemotherapy for advanced gastric cancer

Although recent phase II studies have demonstrated high antitumor activity in the treatment of advanced gastric cancer, no significant survival benefit has been clearly demonstrated yet, when compared with 5-FU alone. More recently, a number of new agents including irinotecan and S-1 have demonstrated significant activity against gastric cancer as single agent or in combination with other chemotherapeutic agents. A phase III trial of 5-FU alone versus irinotecan plus cisplatin versus S-1 alone in advanced gastric cancer patients will be initiated in Japan Clinical Oncology Group (JCOG) within a few months. These new regimens have a potential becoming a new standard chemotherapy for the treatment of gastric cancer. The patients with peritoneal dissemination has usually not yet evaluated and explored from clinical study because of risk of toxicity and having no measurable disease. A next randomized phase III trial comparing 5-FU alone with sequential methotrexate and 5-fluorouracil in patients with peritoneal metastasis will be initiated in JCOG next year. The development of molecular biology has demonstrated the molecular mechanisms of chemoresistance or chemosensitivity, as well as a number of molecular targets against cancer cells. To date, many molecular targeted agents are being evaluated in various stages of clinical testing. These advances may provide a possibility of tailor made treatment.     

Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: A combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1. RESULTS: A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%. CONCLUSIONS: Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer.     

A case of long survival of a scirrhous gastric cancer patient with esophageal invasion and peritoneal dissemination through chemotherapy and palliative surgery

We report a case of advanced scirrhous gastric cancer treated by operation and chemotherapy for over four years. The patient was a 54-year-old female who had suffered from gastric cancer with esophageal invasion. She underwent total gastrectomy with D2 dissection. Operative findings revealed peritoneal dissemination, and it resulted in non-curative resection. After surgery, combination chemotherapy with low-dose CDDP administered intraperitoneally and S-1, combination chemotherapy with paclitaxel and 5-FU, and then combination chemotherapy with docetaxel and S-1 were sequentially performed. She also underwent palliative surgery for intestinal obstruction resulting from carcinomatous peritonitis. She achieved long survival with good quality of life(QOL)by multidisciplinary therapy of chemotherapy and surgical operation.     

Efficacy of weekly administration of paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination

We report 3 gastric cancer patients with peritoneal dissemination who failed to take TS-1 due to adverse effects and who were successfully treated with weekly paclitaxel administered intravenously. The patients were 2 men and 1 woman from 73 to 82 years in age. The histological types of gastric cancer were undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80 mg/m2) after short premedication was continued for 3 weeks followed by 1 week rest. Clinical symptoms, including ascites and intestinal obstruction, improved only after administration of 1 cycle in all patients. Except for 1 event with grade 3 neutropenia, no major adverse reactions were observed. Weekly administration of paclitaxel may be a promising chemotherapy for controlling peritoneal metastasis and improving the quality of life of patients with advanced or recurrent gastric cancer.     

Irinotecan monotherapy offers advantage over combination therapy with irinotecan plus cisplatin in second-line setting for treatment of advanced gastric cancer following failure of fluoropyrimidine-based regimens

The optimal regimen of chemotherapy for gastric cancer in a second-line setting remains to be clarified. The aim of this retrospective study was to evaluate the efficacy and safety of second-line irinotecan treatment. A total of 134 patients with gastric cancer who had received prior chemotherapy with fluoropyrimidine-based regimens were treated with irinotecan (150 mg/m(2) on days 1 and 15) alone every 4 weeks (Arm I) or irinotecan (70 mg/m(2) on days 1 and 15) plus cisplatin (80 mg/m(2) on day 1) every 4 weeks (Arm IP) between April, 2004 and March, 2009. Patient characteristics, response rate, progression-free survival, overall survival and safety were investigated. Of 134 patients with recurrent or unresectable gastric cancer, 92 were treated in Arm I and 42 patients in Arm IP. Overall response rate in Arm I was 8.1%, compared with 20.0% in Arm IP (P=0.65). Median progression-free survival (Arm I vs. IP; 2.6 vs. 2.7 months, P=0.73) and median overall survival (Arm I vs. IP; 9.8 vs. 8.0 months, P=0.67) did not differ between the two treatment groups. Neutropenia, leukopenia and anorexia were the most common grade 3/4 adverse events, occurring significantly more frequently in Arm IP than in Arm I (P<0.05). Irinotecan may be a key agent, and serial irinotecan monotherapy is more beneficial as compared to irinotecan plus cisplatin in the treatment of advanced gastric cancer in second-line settings. Irinotecan monotherapy is beneficial compared to irinotecan plus cisplatin in second-line settings for the treatment of advanced gastric cancer refractory to fluoropyrimidine-based regimens.     

JCOG trials of systemic chemotherapy for unresectable or recurrent gastric cancer

From the late 1980s to the early 1990s, the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group (GIOSG/JCOG) conducted several phase II studies, some of which evaluated oral fluoropyrimidines and others of which introduced Western regimens to Japanese patients. Thereafter, in the phase III study JOCG9205 comparing 5-fluorouracil (5-FU), 5-FU plus cisplatin (CDDP) (FP), and uracil and tegafur (UFT) plus mitomycin (UFTM), neither FP nor UFTM showed a survival benefit over 5-FU alone. Whereas irinotecan (CPT-11) and S-1 (new oral fluoropyrimidine) were developed with promising action against gastric cancer in the late 1990s, these agents cannot be used for patients with impaired oral intake and bowel passage caused by severe peritoneal metastasis. Sequential methotrexate (MTX) and 5-FU (MF) therapy showed substantial action against peritoneal metastasis. Thus, GIOSG/JCOG followed different treatment strategies according to the presence or absence of severe peritoneal metastasis. The phase III study JCOG9912, comparing 5-FU, CPT-11 plus CDDP, and S-1, showed a highly significant noninferiority of S-1 to 5-FU in overall survival associated with acceptable toxicities and concluded that S-1 should be considered for the standard chemotherapy for gastric cancer without severe peritoneal metastasis. For patients with severe peritoneal metastasis, the phase III study JCOG0106 compares MF to 5-FU. In that study, patient enrollment has been completed and a final analysis is planned at the end of 2008. The randomized phase II study JCOG0407 compares the best available 5-FU with weekly paclitaxel after failure in first-line chemotherapy containing 5-FU.     

Chemotherapy for metastatic disease: review from JCOG trials

The Gastrointestinal Oncology Study Group of Japan Clinical Oncology Group (GIOSG/JCOG) has conducted several clinical trials to establish standard chemotherapy for unresectable or recurrent gastric cancer. From the late 1980s to early 1990s, two phase II studies by JCOG evaluated oral fluoropyrimidines, and others introduced Western chemotherapy regimens. Thereafter, the first phase III study (JCOG9205), comparing 5-fluorouracil (5-FU), 5-FU plus ciplatin (CDDP) (FP), and uracil and tegafur (UFT) plus mitomycin (UFTM), could not show a survival benefit of either FP or UFTM over 5-FU alone. In the late 1990s, new active agents such as irinotecan (CPT-11) and S-1 (new oral fluoropyrimidine) showed promising results in their phase II trials. The latest phase III study (JCOG9912), comparing 5-FU, CPT-11 plus CDDP, and S-1, showed significant noninferiority of S-1 to 5-FU in overall survival, associated with a better response rate and progression-free survival and acceptable toxicities, and concluded that S-1 should be considered for the standard chemotherapy of unresectable or recurrent gastric cancer. Simultaneously, another Japanese phase III trial comparing S-1 with S-1 plus CDDP showed a survival benefit of S-1 plus CDDP. At present, S-1 plus CDDP is recognized as standard chemotherapy for unresectable or recurrent gastric cancer, and new treatment with molecular target agents is under development.     

Clinical development of S-1 (TS-1) for advanced gastric cancer

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.     

Re-evaluation of phenotypic expression in undifferentiated-type early gastric adenocarcinomas using mucin core protein and CDX2

Background

Undifferentiated-type early gastric adenocarcinomas are generally classified into two groups: pure undifferentiated-type adenocarcinomas, which naturally develop as undifferentiated-type without a glandular component; and mixed differentiated/undifferentiated-type adenocarcinomas, which are associated with some vestigial glandular component and presumably develop from differentiated-type adenocarcinoma. The differences in phenotypic expression between these two groups were examined using mucin core protein and CDX2.

Methods

A total of 210 lesions of undifferentiated-type early gastric adenocarcinoma less than 25 mm in diameter were classified into four categories (gastric type, gastrointestinal type, intestinal type, and null type) based on their MUC5AC, MUC6, MUC2, and CDX2 immunoprofiles.

Results

Gastric type was significantly (p < 0.01) decreased and gastrointestinal type was significantly (p < 0.01) increased both in pure undifferentiated-type adenocarcinomas and in mixed differentiated/undifferentiated-type adenocarcinomas when CDX2 was applied to mucin core protein. In the pure undifferentiated-type adenocarcinomas, gastric type decreased and gastrointestinal type increased as tumor size increased (p < 0.05). In contrast, in the mixed differentiated/undifferentiated-type adenocarcinomas, gastrointestinal type was most common even in small-sized (≤10 mm) carcinomas and was generally stable regardless of tumor size. In submucosal carcinomas, gastrointestinal type decreased and gastric type and intestinal type increased during carcinoma invasion from the intramucosal to submucosal parts (p < 0.05). The positivity rates for all phenotypic markers, especially gastric markers, tended to decrease during submucosal invasion.

Conclusions

CDX2 is a sensitive marker for assessing intestinal phenotypic expression, and it is likely that there are two different pathways of tumor progression in undifferentiated-type adenocarcinoma of the stomach, according to phenotypic expression.     

Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis

BackgroundA phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal metastasis.Patients and methodsGastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m² and i.p. at 20 mg/m² on days 1 and 8. S-1 was administered at 80 mg/m²/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety.ResultsForty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1–23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%).ConclusionCombination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.     

Phase I/II study of a 3-week cycle of irinotecan and S-1 in patients with advanced colorectal cancer

The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan is expected to be a promising regimen for advanced colorectal cancer. This study was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with S-1 in a 3-week cycle regimen and to observe the safety and efficacy for patients with previously untreated advanced colorectal cancer. Eighty milligrams per m(2) of S-1 was given orally for 14 consecutive days and escalated doses of irinotecan were administered on days 1 and 8 every 3 weeks in the phase I trial. Forty patients were treated at the RD during the phase II trial. Forty-three patients were enrolled between February 2005 and March 2007. The dose-limiting toxicity was diarrhea and abdominal pain. The MTD of irinotecan was 100 mg/m(2) and the RD was determined to be 80 mg/m(2) of irinotecan combined with 80 mg/m(2) of S-1. The phase II trial showed that 22 of 40 patients achieved a complete or partial response and eight had stable disease. The overall response rate was 55.0%. The median progression-free survival time and median survival time were 6.7 and 21 months, respectively. There were no treatment-related deaths. The main toxicities were leukopenia, neutropenia, anorexia and diarrhea. This study suggests the combination of irinotecan and S-1 repeated every 3 weeks is tolerable and effective for patients with previously untreated advanced colorectal cancer.     

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

Background

This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy.

Methods

Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m² on day 1 and S-1 was administered orally at 80 mg/m² for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit.

Results

Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively.

Conclusion

This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.     

Combination therapy with S-1 and irinotecan (CPT-11) for advanced or recurrent gastric cancer

S-1 and irinotecan (CPT-11) are active agents against gastric cancer. Some preclinical studies have demonstrated the theoretical background of combination therapy with S-1 and CPT-11 for gastric cancer. Based on these findings, several phase I/II studies of this combination therapy, which has been proposed as a candidate of standard treatment for advanced or recurrent gastric cancer in Japan, have been conducted. Although there were slight differences in the administration schedules of the combination therapy with S-1 and CPT-11 in these phase II studies, the response rates were more than 50%, and the median survival time (MST) exceeded 1 year. Also, good safety profiles were reported. These results warranted a further, phase III, study to define the efficacy of the combination in improving survival. In a phase III study (GC0301/TOP 002 trial), the response rate, the 1-year survival rate, and the MST in the arm with combination therapy of S-1 and CPT-11 were better than these parameters in the S-1 monotherapy arm. However, at 1.5-year follow-up, the overall survival (OS) in the combination therapy of S-1 and CPT-11 arm did not exceed that in the S-1 monotherapy arm [P = 0.23; hazard ratio (HR), 0.89]. As 22% of the patients were censored, further follow-up is needed to determine the OS with more precision. But, of note, in the SPIRITS trial, combination therapy with S-1 and cisplatin (CDDP) significantly prolonged OS compared to S-1 monotherapy (P = 0.037; HR, 0.77), suggesting that CPT-11 may not be the best partner to use in combination with S-1 at present.     

Combination therapy with S-1 and irinotecan (CPT-11) for advanced or recurrent gastric cancer

S-1 and irinotecan (CPT-11) are active agents against gastric cancer. Some preclinical studies have demonstrated the theoretical background of combination therapy with S-1 and CPT-11 for gastric cancer. Based on these findings, several phase I/II studies of this combination therapy, which has been proposed as a candidate of standard treatment for advanced or recurrent gastric cancer in Japan, have been conducted. Although there were slight differences in the administration schedules of the combination therapy with S-1 and CPT-11 in these phase II studies, the response rates were more than 50%, and the median survival time (MST) exceeded 1 year. Also, good safety profiles were reported. These results warranted a further, phase III, study to define the efficacy of the combination in improving survival. In a phase III study (GC0301/TOP 002 trial), the response rate, the 1-year survival rate, and the MST in the arm with combination therapy of S-1 and CPT-11 were better than these parameters in the S-1 monotherapy arm. However, at 1.5-year follow-up, the overall survival (OS) in the combination therapy of S-1 and CPT-11 arm did not exceed that in the S-1 monotherapy arm [P = 0.23; hazard ratio (HR), 0.89]. As 22% of the patients were censored, further follow-up is needed to determine the OS with more precision. But, of note, in the SPIRITS trial, combination therapy with S-1 and cisplatin (CDDP) significantly prolonged OS compared to S-1 monotherapy (P = 0.037; HR, 0.77), suggesting that CPT-11 may not be the best partner to use in combination with S-1 at present.     

Paclitaxel-resistant recurrent gastric cancer responsive to docetaxel: a case report

We present the case of a 58-year-old man who underwent distal gastrectomy for Stage III A advanced gastric cancer, identified as poorly-differentiated adenocarcinoma. He was diagnosed with recurrent peritoneal metastasis 11 months after surgery. S-1(80mg/m / 2)was administered as first-line chemotherapy, followed by weekly paclitaxel(80mg/m2)as secondline chemotherapy. Although a partial response was obtained, a peritoneal tumor in the upper abdomen, ascites, and an elevation in the serum carcinoembryonic antigen(CEA)level were observed. As the tumor proved resistant to paclitaxel, making the treatment ineffective, bi-weekly docetaxel(45mg/m2)was initiated. The tumor showed a partial response, the ascites disappeared, and the serum CEA level decreased. The time to progression was seven months until the appearance of ileus and ascites due to tumor re-growth. This paclitaxel-resistant gastric cancer with peritoneal recurrence proved responsive to docetaxel as third-line chemotherapy. Docetaxel may be active against gastric cancer that is resistant to paclitaxel because of the different effects of these two agents. Further clinical studies on the efficacy of docetaxel against paclitaxel-resistant gastric cancer are needed.     

Combination chemotherapy of S-1 and taxanes in Korea

Various combination treatments incorporating S-1 are undergoing clinical trials in Korea, especially combinations with taxane, oxaliplatin, or irinotecan. In a phase I study to estimate the maximum tolerated dose of docetaxel in combination with S-1 administered at a fixed dose of 40 mg/m² twice daily on days 1–14 of each 3-week cycle in patients with advanced gastric cancer, 60 mg/m² docetaxel was declared to be the maximum tolerated dose. A phase I/II study of the same schedule of combination chemotherapy with S-1 plus docetaxel reported doses of S-1/docetaxel of 40/75 mg/m² as the maximum tolerated dose. In a phase I study of S-1 plus weekly docetaxel, the patients received variable doses of docetaxel administered intravenously over 1 h on days 1 and 8 and S-1 administered on days 1–14 of each 3-week cycle. The maximum-tolerated doses of S-1 and docetaxel were determined to be 45 mg/m² and 35 mg/m² in this study. A phase I/II study of docetaxel plus S-1 combination chemotherapy from Korea reported a response rate of 43.3%. Also, a phase II study of paclitaxel plus S-1 as first-line therapy in patients with advanced or relapsed gastric cancer showed an overall response rate of 49%. The most frequent significant toxicities in combination chemotherapies with taxane plus S-1 were neutropenia and febrile neutropenia. However, nonhematological toxicities were mild to moderate. A taxane plus S-1 combination regimen could be a new standard regimen for advanced gastric cancer, given its significant activity and favorable toxicity pattern.     

胃硬化型癌的特征与治疗

胃硬化型癌是进展期胃癌中的特殊类型,伴随间质高度纤维化和癌细胞广泛浸润的胃癌。大体类型主要是Bor? rmann4型癌,组织学类型以低分化腺癌、印戒细胞癌为主体。以胃壁肥厚、狭窄、易产生腹膜转移和高度的淋巴结转移为特征,恶性程度高,预后不佳。手术疗法效果有限,但腹膜转移所致的肠梗阻、尿路梗阻需行姑息性手术。可治愈性切除的病例,积极的R0切除和S-1的术后化疗是必要的。S-1/CDDP术前化疗将是可期待的方法。非治愈切除的病例化疗为第一选择。除此之外,针对胃硬化型癌的生物学恶性度,尤其是腹膜转移的控制,腹腔内化疗的有用性倍受期待。另外,bevacizumab分子靶向治疗,ad- enovirus的基因治疗等研究性的治疗期待其结果。      

A case of S-1-resistant recurrent gastric cancer successfully treated with weekly administration of paclitaxel

We report a case of recurrent gastric cancer with peritoneal dissemination and paraaortic lymph node metastases, successfully treated with weekly administration of paclitaxel. The patient was a 63-year-old man who underwent distal gastrectomy with lymph node dissection for advanced gastric cancer in February 2005. After the operation, adjuvant chemotherapy with S-1 was started and continued. He complained of abdominal distention, anorexia and nausea in April 2006. Therefore, paclitaxel (PTX) was administered at a dose of 60 mg/m(2)/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and abdominal X-ray findings showing intestinal obstruction disappeared after 2 courses. CT scan revealed metastatic lymph nodes were reduced after 3 courses. Grade 1 peripheral neuropathy and grade 2 leukocytopenia were noted, but no serious adverse reaction appeared. Weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1-resistant recurrent gastric cancer.