Palliative chemotherapy for advanced gastric cancer

Wöhrer, Stefan; Raderer, Markus; Hejna, Michael

doi:10.1093/annonc/mdh422

Cited by 153 publications

(119 citation statements)

References 90 publications

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“…The survival time for gastric cancer patients receiving the best supportive care is 3-5 months. In addition, although tumor reduction was observed in only one patient, these results are not inferior compared with those of reports of secondline chemotherapy for advanced gastric cancer [23][24][25]. The CTL response was significantly stronger in four patients, with the resulting prognosis also being longer than in the remaining two patients.…”

Section: Discussioncontrasting

confidence: 50%

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

et al. 2013

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Background Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer. Methods LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course. Results LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient.Conclusions LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/ Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).

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Section: Discussioncontrasting

confidence: 50%

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

et al. 2013

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“…Cytotoxic chemotherapy including 5-fluorouracil (5-FU) is the most effective means of providing survival benefits and improvements in quality of life compared with best supportive care (Wöhrer et al, 2004). However, these improvements have been modest, at best, and thus far no combination has clearly provided a survival advantage over single agent 5-FU (Ohtsu, 2005).…”

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confidence: 99%

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

et al. 2006

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The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically-or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m À2 ) and oral S-1 at a fixed dose of 40 mg m À2 twice daily on days 1 -14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m À2 , with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m À2 in combination with S-1 40 mg m À2 b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31 -61%) and 14.0 months (8.3 -17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.

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“…In advanced gastroesophageal cancer, irinotecan has been studied in phase II trials as a single agent and in combination with various other agents, including FU and cisplatin. Single-agent response rates are around 20%, although rates of up to 60% have been reported for irinotecan combined with cisplatin (Kohne et al, 2003;Wohrer et al, 2004).…”

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confidence: 99%

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

et al. 2006

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We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m À2 on day 1; capecitabine 850 mg m À2 12-hourly on days 1 -9. Level 2: as level 1 but capecitabine 1000 mg m À2 . Level 3: as level 2 but irinotecan 180 mg m À2 . Level 4: as level 3 but capecitabine 1250 mg m À2 . In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3 -4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16 -52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

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Palliative chemotherapy for advanced gastric cancer

Cited by 153 publications

References 90 publications

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

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