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.

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.

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

OBJECTIVE: There 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). METHODS: Surgically 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. RESULTS: The 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 microg/ml (IR(20)) 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 IR(20) 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 microg/ml. CONCLUSION: HDRA 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.

[Safety and efficacy of weekly paclitaxel followed by FEC100 as primary systemic therapy for breast cancer].

The efficacy and safety of primary systemic therapy with weekly paclitaxel (wPTX; 80 mg/m2) followed by FEC100 (cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, 5-fluorouracil 500 mg/m2)were investigated in 52 patients with stage I-III A locally advanced breast cancer. Clinical response was complete in 30 patients (58%) and partial in 19 patients (37%). Pathological complete response was found in 23 primary lesions and 17 sentinel and/or sampling lymph nodes. No patients developed progressive disease and major adverse events except for febrile neutropenia in ten patients. These results showed that primary systemic therapy with wPTX followed by FEC100 is a feasible therapeutic option for breast cancer.

Data acquisition for the histoculture drug response assay in lung cancer.

OBJECTIVE: Application of the histoculture drug response assay for lung cancer was investigated by using data acquired from lung cancer specimens. METHODS: From May 1994 through February 2005, histoculture drug response assay data were obtained from 359 lung cancer specimens held in our institute. We examined chemosensitivities of the tissues to cisplatin, doxorubicin, mitomycin C, 5-fluorouracil, docetaxel, paclitaxel, etoposide, irinotecan, and gemcitabine. Cutoff inhibition rates were determined with each drug for non-small cell lung cancer and were used to calculate predictabilities for chemotherapy responses. RESULTS: The evaluability of the histoculture drug response assay was high at 97.4%. Good predictability, including true-positive and true-negative rates of 73.2% and 100%, respectively, with an accuracy of 83.0%, was observed. CONCLUSION: The histoculture drug response assay appears to be applicable to non-small cell lung cancer for the prediction of responses to chemotherapy.

Radiofrequency ablation therapy in patients with breast cancers two centimeters or less in size.

BACKGROUND: Non-surgical ablation is an attractive approach as a local control method for breast cancer. The purpose of this study was to investigate the complications and efficacy of radiofrequency ablation (RFA) therapy for breast cancer. METHODS: A total of 52 patients with breast cancer were enrolled. The mean tumor size was 1.3 cm (range, 0.5-2.0 cm). Under general anesthesia, RFA was done with a Cool-tip RF system after sentinel node biopsy. All patients received one session of RFA, for a maximum time of 30 minutes for the first 29 patients and 15 minutes for the following 23 patients when so-called 'break', i.e. stopping the delivery of radiofrequency, did not occur. Postoperative cytological evaluation was done 3-4 weeks after operation. Adjuvant therapy consisted of chemo- and/or endocrine-therapy and radiotherapy (50 Gy). RESULTS: The mean time of RFA was 12 minutes (5-25 minutes). One patient (2%) was troubled with a skin burn just above the ablated field. No patient had viable cancer cells on post-operative cytological evaluation. No recurrence developed 15 months on the average after RFA (6-30 months). Cosmesis after RFA was excellent in 43 patients (83%), good in 6 (12%), and fair in 3 (6%). CONCLUSION: RFA can be safely used for breast cancer and provides good local control and excellent cosmesis to patients with small breast cancers.