Koma Naito

Histoculture drug response assay for gefitinib in non-small-cell lung cancer

ObjectiveThere are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA).MethodsSurgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib.ResultsThe HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 μg/ml (IR20) in adenocarcinoma without smoking (39.2% ± 35.1%, n = 6) was higher than that with smoking (2.2% ± 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% ± 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR20 values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%–50% appeared to be suitable for a concentration of 20 μg/ml.ConclusionHDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.

Epidermal Growth Factor Receptor Mutations Are Associated with Docetaxel Sensitivity in Lung Cancer

Introduction: A recent large randomized controlled trial revealed that patients with lung cancer with epidermal growth factor receptor (EGFR) mutations had better prognoses when treated with the EGFR-tyrosine kinase inhibitor, gefitinib, than with cytotoxic chemotherapeutic agents. Lung cancer with EGFR mutations is highly sensitive to EGFR-tyrosine kinase inhibitors. The previous trial implied that EGFR mutations might be predictive of the response to cytotoxic chemotherapy. Methods: Forty-six tumor tissue specimens (32 adenocarcinomas and 14 nonadenocarcinomas) were obtained from patients with lung cancer who underwent surgical resection. EGFR mutations were detected using polymerase chain reaction-invader assay. A histoculture drug response assay was used as an in vitro drug sensitivity test. The inhibition rates of cisplatin, docetaxel (DOC), vinorelbine, and gemcitabine were measured. Results: Sensitizing EGFR mutations were detected in samples from 14 patients, all with adenocarcinomas. The inhibition rate of cisplatin in tumors with EGFR mutations (group M) was 34.8 ± 15.5%, which was significantly lower (p = 0.0153) than in wild-type tumors (group W; 46.6 ± 14.0%). The inhibition rate of DOC in group M (18.8 ± 13.4%) was also significantly lower (p = 0.0051) than in group W (35.4 ± 19.1%). There were no significant differences in inhibition rates of gemcitabine and vinorelbine between groups M and W. Inhibition rates of DOC were significantly lower in group M (p = 0.0256) than in group W (32.6 ± 18.4) in samples from patients with adenocarcinoma. Conclusion: The histoculture drug response assay indicated that lung cancers with EGFR mutations were less sensitive to DOC than EGFR wild-type tumors.

Response of meningeal carcinomatosis from breast cancer to capecitabine monotherapy: a case report.

A 62-year-old woman with breast cancer received neoadjuvant chemotherapy followed by breast-conserving surgery and sentinel node biopsy. During adjuvant endocrine therapy with aromatase inhibitor, she developed multiple bone metastases. Thereafter, she received tamoxifen and zoledronate therapy. In May 2011, she developed a tongue deviation and was diagnosed as having meningeal carcinomatosis. The tongue deviation disappeared 3 weeks after taking capecitabine (2,400 mg/day). Magnetic resonance imaging of the brain showed regression of meningeal carcinomatosis. Levels of tumor markers CEA and CA15-3 changed from 96.0 IU/ml and 3.5 ng/ml to 47.0 IU/ml and 1.5 ng/ml, respectively. Progression-free survival with capecitabine monotherapy was 5 months.

Radiofrequency ablation therapy: results in 100 patients with breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #5153 Background: Radiofrequency ablation therapy (RFA) is one of the most minimally invasive approaches for the treatment of hepatic cancers and other solid malignancies. The aim of this study is to assess the safety and local controllability of RFA against breast cancer. Patients and Methods: A total of 100 pts with localized early breast cancer were enrolled. Ductal spreading and/or daughter nodules were preoperatively checked with mammography, ultrasound and MRI. Tumor size was 0.5-2.0cm (median 1.5cm). LeVeen system and Cool-tip RF system was used in 5 pts and 95 pts respectively. One session of RFA was applied to 96 pts, 2 sessions to 4 pts. To avoid skin burn, 5% glucose was injected subcutaneously just above the tumor and the skin was cooled during RFA. After completing RFA, temperatures along the needle tract were measured at 1 cm intervals in 89 pts. All pts underwent cytological and MR-imaging study 3-4 weeks after operation, and received adjuvant radiotherapy (50Gy) to the breast. Results: RFA heated the tumors up to over 60° in 1 pt, 70° in 4 pts, 80° in 21 pts, 90° in 51 pts, and 100° in 13 pts. Skin burn was found in 2 pts over the tumor, and 1 pt at the grounding pads. No major side effects except for skin burn were found. Postoperative cytological and imaging study showed complete ablation of all the target tumors. No pts developed local and distant recurrence for 16-54 months (median 31 months). Discussion: Our RFA procedures can offer good local control without serious adverse events to breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5153.