Relapsed Gastric Cancer Research Articles

Protocol of OGSG 1901: a phase II trial of ramucirumab plus irinotecan for patients with early relapsed gastric cancer during or after adjuvant docetaxel plus S − 1 therapy

BackgroundAlthough docetaxel plus S-1 adjuvant chemotherapy after gastrectomy with D2 lymphadenectomy has been a standard of treatment for stage III gastric cancer, there is no established chemotherapy for patients with recurrence during or within six months after the completion of adjuvant docetaxel plus S-1 therapy.MethodsThe OGSG 1901 trial is a prospective, open-label, multicenter, phase II trial evaluating ramucirumab plus irinotecan for gastric cancer patients with early relapse after adjuvant docetaxel plus S-1 therapy. The key eligibility criteria were: 1) histologically confirmed gastric adenocarcinoma 2) patients who were on docetaxel plus S-1 adjuvant chemotherapy after the confirmation of pathological stage III, 3) patients with early relapse, i.e., recurrence during or within 6 months after the completion of docetaxel plus S-1 therapy, and 4) patient with Eastern Cooperative Oncology Group performance status of 0–1. Irinotecan (150 mg/m2, day 1) and ramucirumab (8 mg/kg, day 1) will be administered every 2 weeks. The primary endpoint is overall survival, and the secondary endpoints are overall response rate, progression-free survival, and safety. The number of patients has been set at 40 based on the threshold and expected median survival times of 7 and 11 months, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods are 2 and 1.5 years, respectively.DiscussionThe results of this trial will indicate whether the ramucirumab with irinotecan regimen has the potential to be a recommended treatment regimen for patients with recurrence gastric cancer during or within 6 months after the completion of adjuvant docetaxel plus S-1 therapy.Trial registrationThis study was registered in the Japan Registry of Clinical Trials (jRCTs05119071, October 6, 2019).

An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in patients with relapsed gastric cancer.

140 Background: Olaparib is a PARP inhibitor that has shown activity in relapsed gastric cancer (GC) when combined with chemotherapy. MEDIOLA assesses the efficacy and safety of a chemo-free combination of olaparib and durvalumab, an anti-programmed cell death ligand-1 (PD-L1) agent in patients (pts) with solid tumors, including relapsed GC (NCT02734004). Methods: Eligible pts had GC that relapsed following platinum-containing therapy. Pts received olaparib 300 mg PO BID for a 4-wk run-in to allow for serial biopsies, followed by combination olaparib and durvalumab (1.5 g IV q 4 wks) until progressive disease (PD) as measured by RECIST 1.1. Tumor measurements were taken at baseline, 4 wks and q 8 wks thereafter. Primary endpoints were disease control rate (DCR) at 12 wks, safety, and tolerability. The secondary endpoints included DCR at 28 wks, objective response rate (ORR), duration of response (DoR), progression-free survival, and OS. Biomarker endpoints included PD-L1 expression and evaluation of tumor infiltrating lymphocytes. Bayesian predictive probability design was used for statistical analysis. Results: Forty pts were included in the safety and 39 in the efficacy analysis. Among 39 pts, median age was 57 yrs (range 28–77). Nineteen pts (48%) had a grade 3 AE; three pts (8%) a grade 4 AE. Most common AEs were anemia, lipase increase, fatigue, dysphagia, hyponatremia, and alkaline phosphatase increase. Ten pts (25%) had immune-mediated AEs, most commonly rash. The ORR was 10%; two pts had complete response; two had partial response. Median DoR was 11.1 months. DCR at 12 wks was 26%. Further efficacy and biomarker data will be presented. Conclusions: The combination of olaparib and durvalumab was tolerable, with no unexpected AEs. All responses occurred after the addition of durvalumab and were durable, suggesting synergistic treatment effect of the combination in some pts. Furthermore, several pts with early PD showed unexpectedly long survival. DCR at 12 wks was below the target (70%) due to a high rate of early PDs following the olaparib run-in. To address the early treatment failures, an upfront addition of more aggressive therapies to the combination should be explored. Clinical trial information: NCT02734004.

P-075 - Dendritic cell vaccine-based immunotherapy in combination with salvage chemotherapy for patients with advanced or relapsed gastric cancer

P-075 - Dendritic cell vaccine-based immunotherapy in combination with salvage chemotherapy for patients with advanced or relapsed gastric cancer

A phase 2 study of fluorouracil/leucovorin in combination with paclitaxel and oxaliplatin as a salvage treatment in patients with refractory or relapsed advanced gastric cancer

The aim of this study was to evaluate the efficacy and safety of paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) as salvage chemotherapy in pretreated advanced gastric cancer. Fifty-two pretreated patients with the advanced gastric cancer were eligible for this study. The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and leucovorin (400 mg/m2), administered simultaneously over a 2-hour infusion period, followed by an infusion of fluorouracil (2400 mg/m2) over a 46-hour period, every 14 days. From an intention-to-treat analysis, overall response rate and stable disease rate were 28·8 and 38·5%, respectively. The median time to progression and overall survival were 4·1 and 7·9 months, respectively. Grade 3 or 4 neutropaenia, thrombocytopaenia, fatigue, and neuropathy were 38·5, 15·4, 17·3, and 15·4%, respectively. The POF regimen is active in pretreated advanced gastric cancer as salvage chemotherapy, with a favourable toxicity profile.

Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis

BackgroundMany patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care. Patients and methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013. ResultsThe search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001] was observed with salvage chemotherapy.When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel. ConclusionThis meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.

Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

BackgroundThe aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans.MethodsThe study was performed as a crossover design, and ten unresectable or relapsed gastric cancer patients were randomly divided into two groups. Group A (n = 5) was started on Rikkunshito (2.5 g three times daily, orally) from the first course of chemotherapy and followed by a second course without Rikkunshito. A treatment with reversed order was performed for Group B (n = 5). All patients received combined chemotherapy with S-1 plus cisplatin. The primary endpoint was the amount of oral intake, and the categories of scales of anorexia, nausea, and vomiting; secondary endpoints included the plasma concentration of acylated ghrelin.ResultsIn the Rikkunshito-on period, no decrease of the plasma concentration of acylated ghrelin induced by cisplatin was observed. The average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period, and the grade of anorexia was significantly lower in the Rikkunshito-on period than in the Rikkunshito-off period.ConclusionRikkunshito appeared to prevent anorexia induced by cisplatin, resulting in effective prophylactic administration of chemotherapy with cisplatin, and patients could continue their treatments on schedule.

Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy: orotate phosphoribosyltransferase expression is associated with treatment outcomes

This study was performed to analyze the impact of protein expression related to fluoropyrimidine and cisplatin metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, orotate phosphoribosyltransferase [OPRT], excision repair cross-complementation 1, Fanconi anemia complementation group D2, glutathione S-transferase P1, and X-ray repair cross-complementing group 1) on treatment outcomes in patients with metastatic or relapsed gastric cancer (MRGC) receiving S-1/cisplatin chemotherapy. Protein expression was measured by immunohistochemistry (IHC). Of the 43 patients who had received S-1 (80 mg/m2/day; days 1-14) and cisplatin (60 mg/m2; day 1) every 3 weeks and had available tissue blocks, IHC was successfully performed in 41 patients. Patients with high OPRT levels in tumor tissues (IHC score≥6) had superior progression-free survival (PFS) (23.3 vs. 14.1 weeks [median]) and overall survival (OS) (72.4 vs. 55.4 weeks [median]) to those with low OPRT levels (IHC score≤5; P-values<.05). Expression levels of other proteins were not predictive of treatment outcomes. In multivariate analysis, both a good performance status and a high OPRT level were independently associated with prolonged PFS and OS. The OPRT expression level may be a good predictive marker in S-1/cisplatin-treated patients with MRGC.

Abstract 1734: MMP-2 as a putative biomarker in body fluid of gastric cancer

Abstract Carcinoembryonic antigen (CEA) and fluid cytology are widely used in patients with gastrointestinal malignancies for evaluating tumor status, but its sensitivity is low and unsatisfactory. In this study, we evaluated the possibility of MMPs, known to promote cancer progression through increasing cancer cell growth, migration, invasion, metastasis and angiogenesis, as a novel biomarker in the body fluid of advanced gastric cancer. Total 135 body fluids (105 ascites, and 24 pleural fluids) from metastatic or relapsed gastric cancer patients diagnosed with peritoneal carcinomatosis at Severance Hospital, Yonsei University from 2000 to 2009 were collected. To determine the cut-off expression level of MMPs, we performed zymography and ELISA using the conditioned media of HT-1080 at various protein concentrations. Ascitic CEA (aCEA) and pleural CEA (pCEA) was measured by EIA. MMP-2 and MMP-9 levels in patient samples were determined with ELISA. Finally, we compared the expression of MMPs with clinical parameters such as fluid CEA, cytology, and survival. Comparing MMPs activity and expression in HT-1080, positive levels of MMP-2 and MMP-9 were 8.59ng/mL and 0.14ng/mL, respectively. Out of 105 ascitic fluids, MMP-2 had a positivity of 93.7%, MMP-9 34.2%, and aCEA 82.9%. Ascitic fluid cytology of 95 patients showed postitive rate of 55.9%. Combining aCEA and MMP biomarkers, the positivity improved; the positivity of MMP-2 and aCEA was 99.1%, while MMP-9 and aCEA was 86.5%. Interestingly, positivity of MMP-2 in aCEA negative patients was 94.7% and 21.1% in MMP-9. To evaluate the role of MMPs as a prognostic marker, the duration of survival was analyzed from the date when ascites was detected until death. The overall median survival in all patients was 62 days. Comparing survival with MMPs expression level, we found a negative correlation between MMP-2 and survival. We observed that patients with a higher MMP-2 expression, ≥ 22.6ng/mL which showed significant MMP-2 activation in zymography, had a shorter survival with a median of 15 days, while lower expression group had a median of 35 days, P &amp;lt; 0.01. In 24 pleural samples, MMP-2 had a positivity of 66.7%, MMP-9 45.8%, pCEA 70.5%, and cytology was 66.7% (n=18). When we combined these markers, MMP-2 and pCEA together increased the positivity to 91.7%, MMP-9 and pCEA 79.2%, MMP-2, MMP-9, and pCEA 91.7%. In conclusion adding MMPs, especially MMP-2, to fluid CEA increased the positivity allowing us to evaluate clinical status more accurately. Also, higher MMP-2 expression showed poor prognosis in advanced gastric cancer with ascites, suggesting the possibility of MMP-2 as a prognostic marker. With further development, MMPs expression in body fluid can be used to detect residual micrometastasis or predict recurrence in peritoneal washing fluid or pelvic fluid. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1734.

Three-weekly S-1 plus cisplatin chemotherapy as first-line treatment for advanced gastric cancer

Combination chemotherapy of S-1 and cisplatin has shown promising activity against advanced gastric cancer, but the schedules and dose intensities of S-1 and cisplatin have not been consistent in several clinical trials. We investigated the efficacy and toxicity of 3-weekly S-1/cisplatin chemotherapy as first-line treatment in metastatic or relapsed gastric cancer (MRGC). Forty-six patients with MRGC were prospectively enrolled. S-1 (80 mg/m(2)/day; days 1-14) and cisplatin (60 mg/m(2); day 1) were administrated every 3 weeks. Among 46 patients who received chemotherapy, one achieved a complete response and 21 achieved a partial response, resulting in an overall response rate (RR) of 48%. Thirteen patients (28%) had stable disease and eight patients (17%) had progressive disease. After a median follow-up duration of 48.3 weeks, the median progression-free survival (PFS) and overall survival (OS) were 21.1 weeks and 68.3 weeks, respectively. Patients with good Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 had prolonged PFS and OS compared with patients with ECOG PS of 2. Common hematologic toxicities were anemia (93%), leucopenia (61%), and neutropenia (61%). However, grade 3/4 anemia, leucopenia, and neutropenia developed in only 11, 9, and 24% of patients, respectively. Grade 3/4 non-hematologic toxicities included anorexia (22%), fatigue (13%), nausea (7%), and diarrhea (7%). No treatment-related mortality occurred. Three-weekly S-1/cisplatin chemotherapy was active and well-tolerated in MRGC patients.

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.

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for patients with advanced or recurrent unresectable gastric cancer

This study was conducted to evaluate the safety and efficacy of S-1 and paclitaxel combination therapy for patients with advanced gastric cancer. Eligible patients had previously untreated advanced or relapsed gastric cancer with measurable lesion(s) and an ECOG PS of 0-2. Treatment consisted of S-1 35 mg/m(2) p.o. b.i.d. on days 1-14 followed by a 7-day off plus paclitaxel 70 mg/m(2) i.v. on days 1 and 8 of a 21-day cycle. Fifty-six patients (M/F = 37/19) were enrolled. The median age was 59 years. The median number of cycles administered was six (range 1-18). Out of the 53 patients evaluated, there was 1 (1.9%) CR, 20 (37.7%) confirmed PRs, 5 (9.4%) unconfirmed PRs, 21 (39.6%) SDs, and 6 (11.3%) PDs. The objective tumor response was 39.6%. The median time to progression was 29 weeks. The median survival was 51 weeks. All 56 patients were assessed for treatment safety. The treatment was well tolerated with grade 3/4 neutropenia in 20%/13%, grade 3 febrile neutropenia in 7%, grade 2/3 diarrhea in 9%/4%, vomiting in 11%/0%, stomatitis in 4%/4%, and neuropathy in 4%/0% of patients. S-1 and paclitaxel combination treatment is an effective regimen with a favorable toxicity profile in patients with advanced gastric cancer.

Irinotecan Combined with 5-Fluorouracil and Leucovorin as Second-line Chemotherapy for Metastatic or Relapsed Gastric Cancer

We analysed the efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) chemotherapy as second-line treatment for metastatic or relapsed gastric cancer (MRGC) in a clinical practice setting. Factors to select patients who may benefit from salvage chemotherapy was also analysed. Patients with MRGC with progression on or within 6 months after discontinuing platinum-based chemotherapy received FOLFIRI as second-line therapy. The FOLFIRI regimen consisted of irinotecan (180 mg/m(2); day 1) combined with leucovorin (200 mg/m(2)), followed by 5-fluorouracil (400 mg/m(2)) as a bolus and 600 mg/m(2) as a 22-h infusion on days 1 and 2 every 2 weeks. Fifty-one patients received a total of 282 courses of chemotherapy. No patients had complete remission (CR), but 9 patients achieved partial remission (PR). Stable disease (SD) was documented in 15 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.2 and 9.1 months, respectively. Toxicities were tolerable and grade 3/4 neutropenia was observed in 49 cycles (17%). In multivariate analysis, patients with less organ involvement by metastasis and good performance status (PS) were independently associated with a longer PFS and OS (P < 0.05). Disease control (CR, PR or SD) after first-line chemotherapy were related to a longer PFS (P = 0.02), but had no effect on OS. FOLFIRI was tolerable and showed modest activity as a second-line therapy in MRGC. Less organ involvement by metastasis or good PS may be optimal selection criteria for patients with MRGC who are suitable for second-line chemotherapy.

A Phase II Study of Leucovorin, 5-FU and Docetaxel Combination Chemotherapy in Patients with Inoperable or Postoperative Relapsed Gastric Cancer

To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotherapy in patients with inoperable or postoperative relapsed gastric cancer. Total 27 patients are enrolled in this study. LV 20 mg/m(2) (bolus), 5FU 400 mg/m(2) (bolus), 5-FU 600 mg/m(2) (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m(2) (1-hour infusion) on day 15 every 4 weeks. Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0 approximately 12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0 approximately 8.5) and the median overall survival time is 11.9 months (95% CI, 4.8 approximately 19.1). The grade 3-4 toxicity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxicity of injection site reaction is observed all patients and the grade 1-2 toxicity of alopecia is observed 60%. LV5FU2 with docetaxel combination chemotherapy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy in patients with advanced or relapsed gastric cancer

4634 Background: S-1 is an oral prodrug of 5-fluorouracil (5-FU) including two modulators to enhance the antitumor effect and to decrease gastrointestinal toxicity. Paclitaxel has the synergistic antitumor effect with 5-FU. This study were planned to evaluate the efficacy and safety of S-1 and paclitaxel combination therapy in advanced gastric cancer. Methods: Eligible patients had untreated advanced or relapsed gastric cancer with measurable lesion(s), histologic proof, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of S-1 35mg/m2 p.o. b.i.d. on days 1–14 plus paclitaxel 70mg/m2 i.v. on days 1&amp; 8 of a 21-day cycle. Measurable and/or unmeasurable lesion was assessed after every 2 courses with RECIST criteria. Results: A total of 56 patients (M/F=37/19) were enrolled. The median age was 59 years with advanced (n=43) and relapsed (n=13) gastric cancer. The common metastatic lesions were abdominal lymph nodes (71%), liver (39%), and peritoneum (21%). Out of 53 evaluable patients, there was 1 (2%) CR, 25 (47%) PRs, 21 (40%) SDs, and 6 (11%) PDs. Objective tumor response was 49%. Median duration of response was 5.4+months after the confirmation of response. Median follow-up was 9.6 month. Median PFS was 7.7 months and median survival was 14.6 months. Median number of cycle was 6 (range, 1–14). The relative dose intensity of S-1 and paclitaxel was 93%, both. The most common causes of delayed cycle and dose reduction were neutropenia and diarrhea, respectively. All 56 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 14%/5%, grade 3 febrile neutropenia in 5%, grade 2/3 N/V in 21%/0%, anorexia in 18%/2%, diarrhea in 9%/4%, stomatitis in 7%/4%, and neuropathy 7%/0% of patients. Conclusions: S-1 and paclitaxel combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with advanced gastric cancer. (This study was partially supported by a grant of the Korea Health 21 R&amp;D Project, Ministry of Health &amp; Welfare, Republic of Korea (0412-CR01–0704–0001)) No significant financial relationships to disclose.

Phase II Trial of Low-dose Paclitaxel and Cisplatin in Patients with Advanced Gastric Cancer

Paclitaxel has shown promising activity in gastric cancer and has synergism with cisplatin. This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel (145 mg/m(2)) plus cisplatin chemotherapy in metastatic or relapsed gastric cancer. Chemotherapy-naïve patients with metastatic or relapsed gastric cancer were enrolled. Paclitaxel 145 mg/m(2) was administered intravenously over 3 h, followed by cisplatin 60 mg/m(2) on Day 1 every 3 weeks in the outpatient setting. Of 39 patients enrolled, 17 (44%) had partial responses. Twelve (31%) had stable disease and eight (21%) progressive disease. Two patients (5%) were not evaluable because of early drop-out. The median time to progression was 4.7 months and the median overall survival was 12.1 months. The most common hematologic toxicity was anemia (41%). Grade 3/4 neutropenia and thrombocytopenia developed in 14 and 3%, respectively. The most common non-hematologic toxicities were peripheral neuropathy (43%) and emesis (43%). Grade 3/4 non-hematologic toxicities included emesis (11%), peripheral neuropathy (3%), diarrhea (3%) and hepatotoxicity (3%). Low-dose paclitaxel and cisplatin chemotherapy was active and well-tolerated in chemotherapy-naïve gastric cancer patients. This regimen seems to have comparable efficacy to previously reported higher-dose paclitaxel plus cisplatin-containing regimens and fewer toxicities.

Phase II study of low-dose paclitaxel and cisplatin as second-line therapy in 5-fluorouracil and platinum pretreated gastric cancer

4194 Background: Paclitaxel has shown promising activity as a single agent in gastric cancer and has synergism with cisplatin in human gastric cancer cell lines. This study was performed to evaluate the efficacy and toxicity of an outpatient regimen composed of low-dose paclitaxel and cisplatin in patients with metastatic or relapsed gastric cancer who had progressed disease during or after treatment with 5-fluorouracil (5-FU) and platinum compounds. Methods: Patients with documented progression on or within 6 months of 5-FU and platinum-based chemotherapy were enrolled. As second-line treatment, paclitaxel 145 mg/m2 was administered intravenously over 3 hours, followed by cisplatin 60 mg/m2 on day 1 every 3 weeks in the outpatient setting. Results: Between October 2002 and June 2004, 28 patients (25 male and 3 female) were enrolled. As first-line treatment, 24 patients received 5-FU/cisplatin and 4 patients received 5-FU/oxaliplatin/leucovorin. Median age was 62.5 years. Of these patients, 8 (29%) had partial responses. Six (21%) had stable disease and 12 (43%) had progressive disease. Two patients (7%) were not evaluable because of early drop-out from this study due to treatment-related toxicities. With the median follow-up duration of 10.5 months, the median time to progression (TTP) in all patients was 2.9 months (95% confidence interval [CI]: 1.9∼3.9 months) and the TTP in responders was 4.3 months (95% CI: 3.1∼5.5 months). The median overall survival was 9.1 months (95% CI: 7.0∼11.2 months). The most common hematologic toxicity was grade 1∼2 anemia (43%). Grade 3 leucopenia developed in 7% and no other grade 3∼4 hematologic toxicity or neutropenic sepsis were observed. The most common non-hematologic toxicities were peripheral neuropathy (32%) and emesis (25%). One case (4%) of grade 4 emesis and 2 cases (7%) of grade 3 peripheral neuropathy were developed; 2 (7%) patients were dropped out from this study due to toxicities. No other grade 3∼4 non-hematological toxicities were observed. Conclusions: As second-line treatment, low-dose paclitaxel and cisplatin chemotherapy in the outpatient setting was active and had acceptable toxicities. No significant financial relationships to disclose.

Modified ECF/wPELF in advanced gastric cancer. Results of a phase II trial

4170 Background. Although ECF represents the treatment of choice in advanced gastric cancer, weekly PELF (wPELF) may be considered an interesting alternative schedule in such a subset of patients. We present activity and safety data of a modified-ECF/alternating wPELF, in which a 21-day ECF was alternated with 6 courses of wPELF in advanced gastric cancer. Methods. All the patients with advanced or relapsed gastric cancer were considered eligible and enrolled into the trial. All the patients were treated with cisplatin 60mg/mq on day 1, epidoxorubicin 50mg/mq on day 1 and 5FU 200mg/mq on day 1→21, followed by 6 courses of weekly cisplatin 25mg/mq, epidoxorubicin 10mg/mq, etoposide 40mg/mq, and 24-hours infusion of l-folinic acid 120mg/mq and 5FU 2200mg/mq until progression of the disease or intractable toxicity. G-CSF support was used during wPELF. Results. 29 patients were considered eligible and enrolled into the trial. 22 patients (75.8%) presented a measurable, metastatic disease, and 7 patients (24.2%) an valuable, but not-measurable disease. After a median follow up of 10 months 3 complete responses (10.4%), 6 partial responses (20.7%) and 9 stable diseases (34.4%) were observed, with a median time to progression of 257 days. Till today 22 patients (75.9%) were dead, with a median survival of 229 days and 18 (62%), 15 (51.7%) and 12 (41.4%) patients alive respectively after 6, 9 and 12 months of follow up. Toxicity was mild, with grade III leucopenia in 6 patients (20.7%), grade III-IV neutropenia in 15 patients (51.7%), grade III vomiting in 3 patients (10.3%), grade III diarrhoea in 1 patient (3.4%), grade III mucositis in 1 patient (3.4%). No febrile neutropenia, nor haemorrhagic thrombocitopenia occurred in any patient. Conclusions. The addition of wPELF to ECF seems to add nothing in terms of activity against metastatic gastric cancer; otherwise the high effectiveness in terms of median survival and 1-year survival rate, with the interesting safety make the modified ECF/wPELF an interesting option as first line treatment of gastric cancer for further phase III trials. (Supported by IOR) No significant financial relationships to disclose.

Expression and clinical significance of CD44 in the peripheral blood of patients with castric cancer

Objective: To investigate the clinical significance of cell adhesive molecule (CD44) expression on periphery blood (PB) of patients with gastric cancer. Methods: Both the level of CD44 and the immunocyte phenotype of the lymphocytes of 110 patients with gastric cancer and 100 healthy subjects were examined by flow cytometry, and the results were analyzed pathologically and statistically. Results: The mean of the CD44% in PB of the healthy subjects was 46.14±3.4 and there were no statistic differences for their age and sex. Site of tumor growth: The significant difference (P 10 cm mass (P<0.01) and 7–10 cm mass (P<0.05). Degree of tumor differentiation: The significant difference (P<0.01) was present between the patients with low differentiation gastric cancer and normal individuals. The significant difference (P<0.01) was present between patients with metastatic stage: The significant difference (P<0.01) was present lymph node gastric cancer and normal individuals. Clinical between the patients with advanced or relapsed gastric cancer and normal individuals. Age: The significant difference (P<0.01) was present between the gastric cancer patients under 59 years and normal individuals. Conclusion: The increased level of CD44 in the PB of patients with gastric cancer indicated the possible existence of relapse, advance or metastasis of tumors. When the tumor was poorly differentiated and bigger in tumor mass, the level of CD44% would be higher. Examining the level of CD44 by flow cytometry in the periphery blood of patients with gastric cancer was useful for the prognosis.