ABSTRACT
BACKGROUND: The mean 5-6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy. METHODS: Major eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0-2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80-120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR). RESULTS: A total of 31 patients were enrolled. DCR was 65% [95% confidence interval (CI), 48-100%] and the response rate was 7% (95% CI, 0.7-22%). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95% CI, 2.1-9.3] and 9.9 [95% CI, 7.4-NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26%) and diarrhea (11%), which were manageable by dose reduction/interruption. CONCLUSIONS: SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC. TRIAL REGISTRATION: This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( ID UMIN000009083 ) on 11 October 2012.
Subject(s)
Bevacizumab/administration & dosage , Colorectal Neoplasms/drug therapy , Leucovorin/administration & dosage , Oxonic Acid/administration & dosage , Tegafur/administration & dosage , Administration, Oral , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Drug Combinations , Female , Humans , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Oxonic Acid/adverse effects , Salvage Therapy/methods , Tegafur/adverse effects , Treatment OutcomeABSTRACT
Here, we report a patient with gastric adenosquamous carcinoma (ASC) with human epidermal growth factor receptor-2 (HER2) overexpression who was successfully treated with trastuzumab-based chemotherapy. The patient was a 66-year-old man preoperatively diagnosed with gastric adenocarcinoma with no evidence of distant metastases. On histopathological examination, the curatively resected tumor was identified as ASC with mixed adenocarcinoma and squamous cell carcinoma components. Multiple liver metastases developed 2.5 months after surgery. Because immunohistochemical staining for HER2 was strong in both components, combination chemotherapy with capecitabine, cisplatin, and trastuzumab was initiated. A partial response was confirmed after 6 treatment cycles and PET and CT scans performed after 13 cycles revealed disease resolution with no uptake in the metastatic lesions. No evidence of disease progression has been observed 16 months after initial chemotherapy. This report suggests the potential utility of trastuzumab-based chemotherapy for HER2-positive gastric ASC.
ABSTRACT
PURPOSE: The prognostic and predictive values of carbohydrate antigen 19-9 (CA19-9) levels in metastatic colorectal cancer (mCRC) remain unclear. We reviewed all mCRC patients at a single institution to evaluate the relationship between CA19-9 levels and survival. METHODS: Two hundred and fifty-two patients underwent first-line chemotherapy using oxaliplatin-based regimens between April 2005 and December 2009. The relationship between baseline CA19-9 levels and survival was analyzed. Moreover, we evaluated the relationship between baseline CA19-9 levels and clinicopathological factors. RESULTS: One hundred and fifty patients had elevated baseline CA19-9 levels (elevated group), and 79 patients had normal baseline CA19-9 (normal group) levels. Both KRAS and BRAF mutation rates were higher in the elevated group than in the normal group. Elevated CA19-9 level was a poor prognostic factor compared with normal CA19-9 levels (P = 0.0021). In the elevated group, the median survival time with bevacizumab was significantly longer with bevacizumab than without it (median OS, 27.8 vs. 15.3 months, P = 0.0019). However, the median survival time was not different with or without bevacizumab in the normal group (median OS, 36.5 vs. 38.0 months, P = 0.9515). CONCLUSION: Our results suggest that baseline CA19-9 level is an independent prognostic factor in mCRC patients, and it correlated with the KRAS/BRAF mutation status. Bevacizumab exhibits clinical activity only for high CA19-9 levels in mCRC.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CA-19-9 Antigen/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bevacizumab , Cohort Studies , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Retrospective Studies , Survival Analysis , Young AdultABSTRACT
BACKGROUND: The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival. METHODS: We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011. RESULTS: Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5-17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58-3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10-2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16-2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site. CONCLUSIONS: Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.