Hiroko Hasegawa

Effect of S-1 Adjuvant Chemotherapy on Survival following Recurrence and Efficacy of First-Line Treatment in Recurrent Gastric Cancer

Background: As S-1 monotherapy has recently become the standard adjuvant regimen for stage II-III gastric cancer patients after curative gastrectomy in Japan, the question whether adjuvant S-1 affects the subsequent clinical course of relapsed patients has attracted great concern. Patients and Methods: We retrospectively evaluated the effect of adjuvant S-1 on survival following recurrence and efficacy of first-line treatment in patients with recurrent gastric cancer after curative gastrectomy. A total of 89 patients were evaluated. Thirty patients received adjuvant S-1 (cohort A), 10 patients were given adjuvant chemotherapy with other oral 5-FU agents (cohort B) and 49 patients received no adjuvant chemotherapy (cohort C). Results: Median survival time following recurrence was 287 days in cohort A, 451 days in B and 547 days in C, with a significant difference between A and C (p = 0.0034). Response rates of the first-line chemotherapy after recurrence were 6.7, 30.0 and 42.9% in cohorts A, B and C, respectively, with a significant difference between A and C (p = 0.0007). On multivariate analysis, S-1 adjuvant chemotherapy was independently associated with poor prognosis after recurrence (hazard ratio 2.64). Conclusion: S-1 adjuvant chemotherapy significantly reduced survival and response to first-line chemotherapy following recurrence in patients with recurrent gastric cancer.

Efficacy of Second-Line Bevacizumab-Containing Chemotherapy for Patients with Metastatic Colorectal Cancer following First-Line Treatment with an Anti-Epidermal Growth Factor Receptor Antibody

Objective: Anti-epidermal growth factor receptor (EGFR) antibodies and bevacizumab are commonly used, sequentially, as palliative chemotherapies for patients with metastatic colorectal cancer. However, little is known about the efficacy of second-line treatments containing bevacizumab after first-line treatment with an anti-EGFR antibody. Methods: We retrospectively reviewed 128 patients who received second-line bevacizumab-containing chemotherapy and evaluated the effect of prior use of anti-EGFR antibody on the efficacy of the second-line treatment. Results: As first-line treatments, 35 of these patients received only cytotoxic chemotherapy (cohort A), 58 received bevacizumab-containing chemotherapy (cohort B), and 35 received anti-EGFR-containing chemotherapy (cohort C). The median progression-free survival (PFS) with the second-line bevacizumab-containing therapy was 8.3 months in cohort C, 6.9 months in cohort A (hazard ratio [HR], 1.43; 95% confidence interval [CI], 0.83-2.51), and 5.6 months in cohort B (HR, 1.95; 95% CI, 1.18-3.22). Multivariate analysis showed that PFS in cohort C was the same as that in cohort A, but better than that in cohort B. The overall response rate in cohort C (25.7%) was also similar to that in cohort A (20.0%), but better than that in cohort B (10.3%). Conclusions: Prior use of anti-EGFR antibody did not adversely affect the efficacy of subsequent bevacizumab-containing chemotherapy.

Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir

Anemia frequently develops in patients given pegylated interferon, ribavirin (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing reduction or discontinuation of RBV administration. We investigated whether erythropoietin (EPO) could alleviate RBV‐induced anemia to help maintain the RBV dose during the first 12 weeks, the triple therapy phase.

Phase I study of alternate-day administration of S-1, oral leucovorin, and bevacizumab for refractory metastatic colorectal cancer.

e14021Background: S-1 with oral leucovorin (LV) has promising efficacy in gastrointestinal cancer patients (pts) but is linked to high risk of mucositis and diarrhea. Compared with daily administra...

Effect of first-line molecular targeted agents on the efficacy of second-line bevacizumab-containing regimen for metastatic colorectal cancer.

748 Background: Bevacizumab (BV)-containing regimen is a standard second-line chemotherapy(CTX) for patients (pts) with metastatic colorectal cancer (mCRC) regardless of the prior use of BV in the first-line CTX. However, little is known about the efficacy of the second-line BV-containing regimen after first-line CTX with anti-EGFR agents. Methods: We retrospectively evaluated the efficacy of a BV-containing regimen as the second-line CTX for mCRC. The eligibility criteria for the pts included in the study were as follows: ECOG PS 0–2, KRAS wild-type tumors, and refractory to first-line CTX with fluoropyrimidine and oxaliplatin or irinotecan from March 2007 to March 2015. The Kaplan–Meier method with a log-rank test and Cox regression analysis were performed to evaluate the progression-free survival (PFS) of the pts. Results: A total of 123 pts were eligible. The pts’ characteristics were as follows: males/females 73/50, median age 59 years, PS 0-1/2 118/5, LDH levels < 400IU/l / ≥ 400IU/l 91/32, second-l...

Optimal indications for palliative chemotherapy in elderly patients with metastatic or recurrent gastric cancer.

207 Background: Gastric cancer is the second causes of cancer-related deaths in the world and its incidence of advanced gastric cancer (AGC) in the elderly is increasing as a result of increased life expectancy. However, elderly patients have been underrepresented in many kinds of chemotherapy clinical trials. Therefore it is difficult to evaluate the efficacy and safety of chemotherapy for elderly patients and select the appropriate patients aged 70 years or older who are likely to benefit from the chemotherapy. Methods: There were 265 patients with primary unresectable or recurrent gastric cancer treated at our institution between April 2007 and March 2014. Of all, 90 patients aged 70 years or older were retrospectively identified. We evaluated the efficacy of the chemotherapy and prognostic significance of clinico-pathologic factors to identify the optimal indications for chemotherapy. Univariate and multivariate analyses were perfomed on the base-line characteristics such as patient’s performance stat...

Total bilirubin as a predictive marker for irinotecan-induced toxicity in patients with gastrointestinal cancer.

68 Background: Irinotecan (CPT-11) is widely used for the treatment of patients with gastrointestinal cancer. However, CPT-11 can cause severe neutropenia and diarrhea.It has been reported that the AUC of SN-38, an active metabolite of CPT-11, correlated with Pre-treatment serum total bilirubin level (PTB), but there is no criteria of dose setting based on the PTB. Therefore, we retrospectively searched the PTB which can serve as an indicator for dose setting of CPT-11. Methods: We investigated the incidence of neutropenia and diarrhea at the first 28 days in patients with gastrointestinal cancer who were administered CPT-11 alone in Osaka National Hospital from June 2006 to July 2013. Correlation between PTB and grade 3-4 neutropenia or diarrhea were assessed. When toxicity of correlation exists, ROC (receiver operating characteristic) analysis was conducted to explore the cut-off value of the PTB. In addition, the incidence of febrile neutropenia (FN) in the cut-off value was compared. Results: 87 patie...

A phase II study of panitumumab plus irinotecan for metastatic colorectal cancer with wild KRAS, resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese (OGSG1001).

607 Background: Anti-epidermal growth factor receptor (EGFR) antibody therapy showed to be effective in treatment for metastatic colorectal cancer (mCRC) with wild KRAS. Especially, combination chemotherapy with anti-EGFR antibody plus irinotecan is expected more effective than anti-EGFR antibody alone, resistant to irinotecan. We conducted a phase II trial of panitumumab plus irinotecan for mCRC with wild KRAS resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese. Methods: Subjects were mCRC patients with wild KRAS, who showed resistance to fluoropyrimidine, oxaliplatin, and irinotecan and had measurable disease, ECOG PS 0-2. Panitumumab (6 mg/kg) plus irinotecan (same dose as prior irinotecan) was administered every two weeks. This treatment was provided until progression. The primary endpoint was response rate (RR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), response duration, and adverse event (AE). Results: A total of ...

Optimal criteria of treatment change for advanced gastric cancer patients with nonmeasurable peritoneal metastasis alone.

103 Background: Palliative chemotherapy is the mainstay for the treatment of advanced gastric cancer (AGC) patients with peritoneal metastasis. In general, chemotherapy regimen is changed when patients show disease progression on CT scan. However, nearly 40% of these patients have no measurable lesions. It remains uncertain how clinicians can decide the timing of treatment change for AGC patients with non-measurable peritoneal metastasis alone. Methods: There were 217 patients with primary unresectable or recurrent gastric cancer at our institution between April, 2005 and March, 2012. Among them, 50 patients, who had histologically proven non-measurable peritoneal metastasis alone, were retrospectively identified and investigated in this study. They underwent measurements of tumor markers (TM) every month and abdominal CT scan every 2 months. For these 50 patients, chemotherapy regimen was changed based on the following different 2 criteria; 1. elevated TM and/or aggravated clinical symptoms alone (n=21),...

Optimal indications for second-line chemotherapy in advanced gastric cancer.

105 Background: It remains uncertain whether every patient with advanced gastric cancer (AGC) who progresses after first-line chemotherapy should receive second-line chemotherapy. We conducted the present study to identify the optimal indications for second-line chemotherapy. METHODS In this retrospective study, 101 patients were included in univariate and multivariate analyses to identify clinicopathological variables independently associated with longer survival post progression (SPP), defined as the time from recognition of disease progression on first-line chemotherapy to death from any cause or last follow-up. RESULTS Median SPP of all patients was 340 days. On multivariate analysis, both performance status (PS) 2 (hazard ratio (HR), 14.234; 95% confidence interval (CI), 2.766-73.258), serum albumin (Alb) level < 3.5 g/dl (HR, 2.088; 95% CI, 1.047-4.060) at initiation of second-line chemotherapy, and time to progression (TTP) < 170 days on first-line chemotherapy (HR, 2.497; 95% CI, 1.227-5.083) were identified as independent prognostic factors for shorter SPP. Median SPP was 496, 375, and 232 days in patients with 0, 1, and 2 of these 3 negative prognostic factors, respectively (p = 0.0002). CONCLUSIONS The present study suggests that second-line chemotherapy would be less beneficial in patients with 2 or more of the following 3 negative prognostic factors: PS 2, Alb < 3.5 g/dl at initiation of second-line chemotherapy, and TTP < 170 days on first-line chemotherapy.