Chemotherapy For Metastatic Gastric Cancer Research Articles

Second-Line Irinotecan after Cisplatin, Fluoropyrimidin and Docetaxel for Chemotherapy of Metastatic Gastric Cancer

Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in Izmir, Turkey. We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/m(2) on each 21 days. Irinotecan (180 mg/m(2) on day 1), 5-FU (500 mg/m(2) on days 1-2) and leucovorin (LV; 60 mg/m(2) on days 1-2) as a combined regimen were given over a 14 day period. Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression- free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

Expression profiling and long lasting responses to chemotherapy in metastatic gastric cancer

Current palliative chemotherapy (CT) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers, and long-term survivals are anecdotical. Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism, DNA repair and drug resistance can explain the observed individual differences in response to drugs, in survival and in different susceptibility to the toxic effects of CT. The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen. We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer, treated with CT and alive, disease-free, at 66-82 months. Four patients with typical clinical outcome represented the control group. Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance, DNA repair, cell cycle regulation and growth factors signalling. Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response. Expression analysis in long-term survivors revealed a significant upregulation of PTEN, TP63, GADD45a and MAPK1 genes. We found also an upregulation of CYP1A1, CYP3A4 and ERBB4 genes. EGF was found to be down-regulated in long-term survivors. ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients. The present study shed light on a set of genes, which could have a predictive role in survival of patients with metastatic gastric tumors.

Paclitaxel and cisplatin combination chemotherapy for advanced gastric cancer failed to 5-fluorouracil-based chemotherapy.

e14608 Background: There is no standard treatment in patients with metastatic gastric cancer failed to first- line treatment. Taxane is one of novel agents recognized as having significant activity in gastric cancer. We performed a trial to estimate the effectiveness and toxicity of paclitaxel plus cisplatin combination regimen as a salvage chemotherapy for metastatic gastric cancer failed to 5-fluorouracil (5-FU)-based chemotherapy. Methods: Metastatic or recurrent gastric cancer patients failed to 5- FU based treatment (FAM,FL,FP) with an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 were qualified in this trial. Paclitaxel 175mg/m2 was infused over 3 hour, before cisplatin 70 mg/m2 infused over 2 hours on day 1, once every 3 weeks until disease progression or intolerable toxicity was detected. Response to treatment was assessd every three cycles. Results: From October 2004 to December 2008, 31 patients were enrolled in this study. 31 patients were assessable for response. Partial response was observed in seven patients and stable disease in four patients. The response rate was 22.5% (95% confidence interval: 17.4-27.6%). The median survival of all enrolled patients was 26 weeks (range: 8-67 weeks). For a total of 125 cycles of chemotherapy, grade 3 and 4 toxicity was 12.8% for neutropenia, 3.2% for nausea/ vomiting and 1.6% for mucositis. Conclusions: Salvage chemotherapy with paclitaxel plus cisplatin regimen in gastric cancer was effective with acceptable toxicities. No significant financial relationships to disclose.

Feasibility of self‐expandable metallic stent plus chemotherapy for metastatic gastric cancer with pyloric stenosis

Self-expandable metallic stent placement is accepted as palliative therapy for advanced gastric cancer with gastric outlet obstruction, but data are lacking for chemotherapy after self-expandable metallic stent insertion. This study retrospectively compared results between surgery plus chemotherapy and stenting plus chemotherapy for metastatic gastric cancer with pyloric stenosis. Subjects comprised 26 patients who received chemotherapy after surgery or endoscopic stenting for metastatic gastric cancer with pyloric stenosis between April 2000 and December 2007 in four Japanese hospitals. Patients were categorized into two groups: 15 patients who received chemotherapy after surgery for pyloric stenosis (Surgery group); and 11 patients who received chemotherapy after self-expandable metallic stent placement for pyloric stenosis (Stent group). Median survival time and median time to treatment failure were 284 days and 226 days in the Surgery group and 337 days and 247 days in the Stent group, respectively. No significant differences were noted between survival and time to treatment failure. No significant differences were found in median oral intake rate (Surgery, 93.1%; Stent, 93.2%) or median hospital stay rate (Surgery, 24.6%; Stent, 23.7%) during survival. Response rate was 45.5% in the Surgery group and 50% in the Stent group, with no significant difference. Likewise, no significant differences were noted between groups for frequencies of toxicity or complications. The present results suggest that chemotherapy after stenting is as effective and safe as chemotherapy after surgery. Stents may replace surgery in combination therapy with chemotherapy for metastatic gastric cancer with gastric outlet obstruction.

Predictive factors for the efficacy of cetuximab plus chemotherapy as salvage therapy in metastatic gastric cancer patients

We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients. Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA. Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0-10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3-2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4-5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS. Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status.

Survival predictors in second-line chemotherapy for metastatic gastric cancer

e15575 Background: Many patients (pts) with metastatic gastric cancer (MGC) are in good condition after first line chemotherapy (chemo) and are offered further treatment. However there is no established predictor to select pts who will most likely benefit from second line chemotherapy (SLC). Methods: We conducted a retrospective review of all patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma who were treated until death at our institution and died between 01.1994 and 06.2008. Prognostic values of the tumour characteristics, pts characteristics at SLC, previous curative surgery (PCS) and sensitivity to previous chemo were analysed by Cox univariate and multivariate regression for overall survival (OS). Results: 65 pts with MGC were treated at our institution up to their death. Of these, 43 pts (65%) received SLC. 24 pts (55.8%) received CPT-11 based SLC. 4 pts (9.3%) docetaxel-platin, anthracyclines and fluoropyrimidine based SLC. 3 pts (7%) oxaliplatin and 3 pts (9.3 %) other chemo. Median OS from the start of SLC was 30.1 weeks. 25 pts (58.1%) had disease control (response and stable disease) lasting at least 12 weeks under SLC. Potential prognostic variables with their frequencies and prognostic values are listed in the Table . Multivariate analysis showed that PCS was significant predictor for OS (HR=0.46, p<.05). PFS1 of more than 26 weeks was a strong significant OS predictor (HR=0.41, p<.05). Interaction test between PFS1 and PCS was not significant (p=0.48). Conclusions: Benefit from a SLC in MGC is highly related to former sensitivity to first line chemo. This is of major importance in the design of trials in MGC in a second line setting. [Table: see text] No significant financial relationships to disclose.

Chemotherapy After Stenting Is Feasible for Metastatic Gastric Cancer with Pyloric Stenosis

Background: Although surgical treatments such as gastrojejunostomy is the standard palliative treatment for unresectable gastric cancer with gastric outlet obstruction (GOO), self-expandable metallic stent (SEMS) placement has been recently accepted as palliative therapy for those. Chemotherapy for advanced gastric cancer has been positively performed because new drugs such as S-1, irinotecan and taxanes show high response rates. However, data are lacking for chemotherapy after SEMS insertion. This study retrospectively compared results between surgery plus chemotherapy and stenting plus chemotherapy for metastatic gastric cancer with GOO. Patients and Methods: Subjects comprised 26 patients who received chemotherapy after surgery or endoscopic stenting for metastatic gastric cancer with pyloric stenosis between April 2000 and December 2007 in 4 Japanese hospitals. Patients were categorized into 2 groups: 15 patients who underwent surgery for pyloric stenosis and received chemotherapy (Surgery group); and 11 patients with SEMS placement for pyloric stenosis who received chemotherapy (Stent group). Results: No significant differences were noted between Surgery and Stent groups in terms of gender ratio, median age, PS, histological type, location and number of metastases, first-line chemotherapeutic regimen and number of chemotherapeutic regimens used. Median survival time and median time to treatment failure (TTF) were 284 days and 226 days in the Surgery group and 337 days and 247days in the Stent group, respectively. No significant differences were noted between in survival and TTF. No significant differences were found in median oral intake rate (Surgery, 93.1%; Stent, 93.2%) or median hospital stay rate (Surgery, 24.6%; Stent, 23.7%) during survival. Response rate was 45.5% in the Surgery group and 50% in the Stent group, with no significant difference. Likewise, no significant differences were noted between groups for frequencies of toxicity or complications. Conclusions: The present results suggest that chemotherapy after stenting is as effective and safe as chemotherapy after surgery. Stents may replace surgery in combination therapy with chemotherapy for metastatic gastric cancer with GOO.

Chemotherapy for metastatic gastric cancer in Japan

Until the 1990s, there were no chemotherapy regimens with old-generation anticancer agents showing a survival benefit over 5-fluorouracil (FU) alone, and standard chemotherapy for metastatic gastric cancer had not been established. In the late 1990s, several new active agents were developed and some phase III trials with these agents were conducted; the new agent S-1 showed noninferiority to 5-FU in these trials. S-1 plus cisplatin is the first doublet chemotherapy to have shown a survival benefit over monotherapy with S-1. It has been demonstrated that capecitabine and oxaliplatin (OHP) can replace 5-FU and cisplatin (CDDP), offering more convenient treatment options. Thus, combination chemotherapy with an oral fluoropyrimidine (S-1 or capecitabine) and platinum (CDDP or OHP) has been recognized as standard chemotherapy for metastatic gastric cancer all over the world. However, it can be said that none of these new combination chemotherapies have shown remarkable progress from 5-FU plus cisplatin regimens. It is expected that triplet chemotherapy with a taxane; the use of molecular targeting agents; and the establishment of treatment strategies including second line chemotherapy, will lead to remarkable progress in personalized medicine in the near future.

Chemotherapy for metastatic gastric cancer: past, present, and future

Despite the numerous efforts of randomized studies on advanced gastric cancer, no globally accepted standard regimen has yet been established. Two triplet regimens have already demonstrated significant survival prolongation in Western studies. However, the benefit seems to be marginal, and these regimens may be replaced by recently published newer generation regimens for which favorable survival is reported. At present, the combination of 5-fluorouracil (5-FU) and platinum analog is still the most widely accepted standard regimen worldwide: 5-FU can be replaced by S-1 or capecitabine, and cisplatin by oxaliplatin. In Japan, S-1 plus cisplatin is the most reasonable first-line standard, based on recent randomized studies. Some early clinical studies using molecular targeting agents have shown promising activity, particularly in combination with cytotoxic agents for gastric cancer. Several targeting agents such as trastuzumab, bevacizumab, and lapatinib are now under investigation in international randomized studies, including in Japan. These agents have shown a survival benefit in other tumor types. The next-generation targeting agents, including mammalian target of rapamycin inhibitor and a c-Met tyrosine kinase inhibitor, are also being evaluated in early clinical studies in association with biology research. Such agents can be advantageously used in gastric cancer studies, which, because of the ease with which tumor tissues can be obtained by endoscopy and the high incidence of gastric cancer in Japan, might advance the frontiers of biologic therapy. These efforts should result not only in further clinical advances but also in tailored medicine.

Capecitabine and Oxaliplatin Are Effective in Advanced Gastric Cancer

Conventional chemotherapy for metastatic gastric cancer entails a 4- to 5-day infusion of 5-fluorouracil (5-FU) plus cisplatin, with a response rate of

Phase II study of cisplatin, epirubicin, UFT, and leucovorin (PELUF) as first-line chemotherapy in metastatic gastric cancer

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur–uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided doses on days 1–22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24–52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5–7.5 months); overall survival was 9.5 months (95% CI 8.5–13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.

A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy > 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.

Phase II study of cisplatin, epirubicin, oral UFT, and leucovorin as first-line chemotherapy for metastatic gastric cancer

14049 Background: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with cisplatin, epirubicin, oral UFT and leucovorin in patients (Pts) with metastatic gastric cancer. Methods: Pts with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day (d)1, UFT 300 mg/m2 was administered in conjunction with oral leucovorin 30 mg/day in divided daily doses d 1–22, followed by a 7-day rest period. Results: Thirty-nine pts were enrolled in this study. Two achieved a complete response and 13 a partial response, giving an overall response rate of 38.5%. Disease stabilization was achieved in further 16 pts (41%). Median time to progression and median survival were 6.4 and 10.7 months respectively. Grade 3/4 neutropenia, anemia, throbocytopenia, occurred in 10%, 5%, and 2% of pts respectively, and febrile neutropenia occurred in 7 pts (one episode each). Grade 3 diarrhea occurred in 5% of the pts. There were no treatment related deaths. Conclusions: Cisplatin, epirubicin, and oral UFT plus leucovorin, a convenient outpatient regimen, has significant activity and tolerable toxicities in pts with metastatic gastric carcinoma. No significant financial relationships to disclose.

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer

Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m(2 )and cisplatin 75 mg/m(2) were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1-9 cycles). The median age was 56 years (range 31-76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4-53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0-9.0) and the median overall survival was 11.5 months (95% CI, 9.5-13.4). The chemotherapy was generally well tolerated and the most common grade 3-4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.

New HIV protease inhibitors for drug-resistant viruses

The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.

Efficacy and safety study of docetaxel as salvage chemotherapy in metastatic gastric cancer failing fluoropyrimidine and platinum combination chemotherapy

4220 Background: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the 1st line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease; overall response rates (RR) were 17∼25% when used as single agent in the 1st line setting. The action mechanism of D is also different from F or P. We investigated the efficacy of D monotherapy as salvage treatment in AGC failing F and P combination chemotherapy. Methods: Twenty-eight patients with measurable and documented progression within 4 months after F and P containing regimens were included in this study. D was given at a dose of 75 mg/m2 IV every 3 weeks. Patients characteristics are as follows; Male/female 24/4, median age 53(31∼70), median ECOG PS 1(1∼2), peritoneal seeding 36%, liver metastases 54%, elevated ALP level 45%, prior exposure to capecitabine + CDDP 13, 5-FU+CDDP 10, doxifluridine+CDDP 3, S1+CDDP 1, and 5-FU+heptaplatin 1. Median treatment free interval was 42 days (21∼158), and 75% of patients had had progression while receiving F+P and 25% had had progression within 4 months after withdrawal of F+P chemotherapy. Results: At the time of analysis, 24 patients were evaluable for response (refusal after 1st cycle 1, docetaxel anaphylaxis 1, too early to evaluate 2) and 26 patients for safety with 8 patients continuing D treatment. A total of 95 cycles of D were administered with a median of 3 (1∼8) cycles. We observed 5 partial responses (PR) without any complete response for an overall RR of 21% (95% CI, 5∼37). Nine patients showed stable disease and 10 patients progressed. The median time to progression was 2.6 months (95% CI, 1.9∼3.3). The duration of objective PRs were 1.8+, 2.5, 2.3+, 3.2+, and 4.0+ months, respectively. Grade 3/4 febrile neutropenia occurred in 11%. The incidence of grade 2 or worse nonhematologic toxicities are as follows; Mucositis 19%, asthenia 33%, neuropathy 10%, and nail change 14%. Conclusions: Docetaxel monotherapy is active for 2nd line salvage chemotherapy after prior exposure to F and P combination chemotherapy in AGC; The RR is comparable to that achieved in previously untreated patients. No significant financial relationships to disclose.

Current status and future prospects of chemotherapy for metastatic gastric cancer: a review

Although many randomized trials of chemotherapy for metastatic gastric cancer have been reported during the past two decades, no standard regimens worldwide have been established yet. Reference arms vary depending on the region and cultural differences. To date, a combination of 5-fluorouracil (5-FU) and cisplatin is most widely used. However, no confirmation of survival advantage over single-agent 5-FU in a randomized trial has been proved yet, and there remain limitations of efficacy results in older-generation regimens. Recently developed new agents such as irinotecan, taxanes (paclitaxel and docetaxel), and new oral fluorouracil (S-1 and capecitabine) provided more promising results: a response rate over 50% and median survival time (MST) over 10 months in their preliminary combination studies. These newer combination regimens are now being investigated in various randomized phase III studies, which will clarify whether the newer-generation regimens provide survival advantage over older-generation regimens. The MST of the new standard should exceed 11 months to be considered a definite improvement, and overall survival seems to be a more desirable primary end point than progression-free survival in a randomized trial. Molecular targeting agents are another concern to improve the treatment outcomes of this disease and are now under investigation in combination with conventional cytotoxic agents. Both clinical and biological research will be more important in future studies.

Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy

Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy. A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m(2) IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy. A total of 133 cycles of D were administered, with a median of 3.5 (1 approximately 8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8 approximately 5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5 approximately 11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%. Docetaxel, 75 mg/m(2), is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Chemotherapy for Metastatic Gastric Cancer: Results from Clinical Trials in Asia

Chemotherapy for metastatic gastric cancer surely has a survival benefit compared to best supportive care. In the recent decades, some phase III trials have been conducted for metastatic gastric cancer all over the world. However, no chemotherapy regimen has shown a survival benefit with 5-FU alone, and there is no standard treatment. Recently, not a few anti-tumor agents have been developed, including irinotecan, oral pyrimidines, Taxane, and molecular target agents. Many phase I and II trials conducted in Asia have shown their activity both as single agents and in combination. Moreover, phase III trials including these new agents are underway, and some of them are expected to prolong survival and establish a standard treatment for metastatic gastric cancer.

Chemotherapy in metastatic gastric cancer: population-based perceptions and practice patterns of medical oncologists.

Although randomised trials in metastatic gastric cancer have shown a survival benefit from chemotherapy, a significant proportion of medical oncologists do not believe that it prolongs survival or improves quality of life, including those who routinely treat metastatic gastric cancer. There was wide variation in what was considered to be ‘standard therapy’ and a statistically significant difference between what medical oncologists consider ‘standard therapy’ and what they use in every day practice.