A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer.

PURPOSE: Intravenous amifostine 200 mg/m2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. PATIENTS AND METHODS: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of > or =Grade 2 acute xerostomia. RESULTS: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of > or =Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of > or =Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. CONCLUSIONS: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.

Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma:: final time-to-event results from the SUMMIT trial.

BACKGROUND: Bortezomib, a first-in-class proteasome inhibitor, has shown clinical activity in relapsed, refractory multiple myeloma in a pivotal Phase II trial, SUMMIT. METHODS: Patients received bortezomib 1.3 mg/m(2) on Days 1, 4, 8, and 11 followed by a 10-day rest period for up to 8 cycles. Dexamethasone 20 mg on the day of and the day after bortezomib was permitted for suboptimal response. Extended treatment beyond 8 cycles was offered to patients whose physicians felt they would benefit from additional therapy. Follow-up was conducted in all patients for a median of 23 months, an additional 13 months from the original report. RESULTS: Of 202 patients enrolled in SUMMIT, 193 were evaluable for response. Seven (4%) patients achieved a complete response, 12 (6%) achieved a nearly complete response, 34 (18%) achieved a partial response, and 14 (7%) had a minimal response while on bortezomib. The updated median duration of response to bortezomib alone was 12.7 months. The median overall time to progression for all SUMMIT patients was 7 months. For responding patients, the median time to progression was 13.9 months, whereas for those with progressive disease (PD) or who were not evaluable, the median time to progression was 1.3 months. The median overall survival (OS) for all SUMMIT patients was 17.0 months. Whereas the median OS for patients with PD or who were not evaluable was 8 months, the median OS for responding patients was not reached at 23 months of follow-up. CONCLUSIONS: These data demonstrate that treatment with bortezomib results in meaningful long-term benefit for patients with relapsed and refractory myeloma.

Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2(+) metastatic breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. PATIENTS AND METHODS: A phase II, open-label trial of intravenous vinorelbine (30 mg/m(2) on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2(+) metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. RESULTS: Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3(+) = 82% (18/22) response and IHC 2(+) = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. CONCLUSIONS: Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2(+) metastatic breast cancer. Further investigation of this novel regimen is planned.

Weekly paclitaxel in women age 65 and above with metastatic breast cancer.

We evaluated therapy with weekly paclitaxel 80 mg/m2 in metastatic breast cancer patients age > or =65. There was a low incidence of serious toxicities, with similar tolerability profiles in younger and older patients. Response rates and overall survival times were comparable in the two age groups (<65 and > or =65). Weekly paclitaxel therapy is a reasonable option for older patients with metastatic breast cancer.