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Background we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC). Patients and methods treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks. Results forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%. Conclusions TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Background and Objective: Understanding neoadjuvant chemotherapy (NAC) for early breast cancer, the pathological response rate in estrogen receptor (ER)-positive has been low in comparison with those of ER-negative. Therefore, the luminal breast cancer (LBC) must have heterogeneity in response to NAC. We analyzed the patterns of tumor shrinkage after NAC as a surrogate prognostic factor in LBC using MRI. Methods and Results: Of 854 patients who had received NAC in the single institute from Jan. 2000 to Dec. 2009, 265 LBC were retrospectively evaluated for this study. The LBC was defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH Discussion: The tumor shrinkage pattern of MRI could be an important surrogate prognostic factor for NAC in early LBC. Our results suggest that the LBC with non-CS pattern may have the higher heterogeneity which associated with chemotherapy-resistant residual cancer cells.

Eribulin mesylate (eribulin), a novel microtubule-targeted inhibitor, was approved ‘inoperable or recurrent breast cancer’ on April 2011 in Japan. In therapeutic system, trastuzumab is used for patients with HER2-positive breast cancer but the safety of combination of eribulin with trastuzumab is not established. And so, we conducted the clinical phase I study of eribulin in combination with trastuzumab in patients with HER2-positive breast cancer to evaluate dose limiting toxicity (DLT), and investigate tolerability and safety. Six patients with prior chemotherapy including trastuzumab and taxanes for advanced or metastatic breast cancer were evaluated in DLT evaluation periods (for 21 or 28 days after drug administration). Eribulin (1.4 mg/m2) was administered as an IV bolus on days 1 and 8 every 3-week cycle, which is approved dosage and schedule, and trastuzumab was administered as an IV infusion weekly (method A). As a result, no adverse events corresponding to DLT were observed, and the common adverse events were neutropenia and leukopenia. On day 15 after drug administration, one of six patients showed the slight decrease in left ventricular ejection fraction, but it was recovered on day 22. And thus, the combination of eribulin with trastuzumab was tolerable in DLT evaluation periods, and the safety profile in this study was similar to that in the past clinical studies of eribulin monotherapy. On the other hand, since the acute cardiac failure was observed, it was thought that the assessment of cardiac function in the combination of eribulin with trastuzumab should be carried out carefully.