aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer.

BACKGROUND: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. MATERIALS AND METHODS: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). RESULTS: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS). CONCLUSION: Chromosome 8q24.1-q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. IMPLICATIONS FOR PRACTICE: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1-p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

Synchronous rectal and esophageal cancer treated with chemotherapy followed by two-stage resection.

We report a case of 61-year-old male who had synchronous advanced rectal cancer involving the urinary bladder massively associated with multiple liver metastases, and esophageal cancer successfully treated by neoadjuvant chemotherapy followed by two-stage resection. Although complete resection of each of the lesions was considered possible by performing anterior pelvic exenteration, liver resection, and esophagectomy, it might be impossible for the patient to endure the stress of all of these operative procedures at once. Therefore, we planned to perform staged treatment with prioritizing consideration. First, we instituted chemotherapy with the FOLFOX (oxaliplatin + fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior resection combined with cystoprostatectomy and lateral segmentectomy plus partial hepatectomy was performed followed by staged esophagectomy with three-field lymph node dissection. It was possible to use oxaliplatin and cetuximab safely as neoadjuvant therapy not only for advanced rectal cancer but for esophageal cancer, and it was effective.

[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer].

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.