A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study.

PURPOSE: This phase II study was undertaken to define the efficacy and toxicity of pemetrexed in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer who had previously received an anthracycline and a taxane in either the adjuvant or metastatic setting were treated with gemcitabine 1250 mg/m2 (intravenous; days 1 and 8) and pemetrexed 500 mg/m2 (intravenous; day 8) every 21 days. RESULTS: Fifty-nine patients received a median of five cycles (range one to 22) of treatment and were followed until death or for a median of 28 months (range 19.4-36.6) among living patients. Fourteen partial responses for an overall response rate of 24% [95% confidence interval (CI) 16% to 39%] were documented. Nine (15%; CI 5% to 32%) patients had stable disease for >6 months. The median survival time was 10.3 months (95% CI 8.3-18.9) and the 1 year survival rate was 49% (95% CI 38% to 64%). The median time to progression was estimated to be 3.7 months (95% CI 2.3-5.3). The most common grade 3 or 4 toxicities were neutropenia and thrombocytopenia in 83% and 27% of patients, respectively. Fourteen percent of patients experienced febrile neutropenia. Other common grade 3 or 4 non-hematological toxicities included fatigue (17%), dyspnea (15%), rash (7%) and anorexia (5%). CONCLUSIONS: The combination of pemetrexed and gemcitabine is clinically active, with an overall response rate of 24% in patients with metastatic breast cancer who have previously been treated with an anthracycline and a taxane. Myelosuppression (66% grade 4 neutropenia and 14% febrile neutropenia) was the major treatment-related toxicity observed for this combination.

A phase II trial of edatrexate, vinblastine, adriamycin, cisplastin, and filgrastim (EVAC/G-CSF) in patients with non-small-cell carcinoma of the lungs: a North Central Cancer Treatment Group Trial.

Edatrexate is an antifolate agent with improved in vitro antineoplastic activity as compared with methotrexate. A Mayo phase I trial of edatrexate (E), vinblastine (V), doxorubicin (Adriamycin) (A), cisplatin (C), and filgrastim (GCSF), (EVAC-GCSF) showed promising antineoplastic activity in non-small-cell lung cancer (NSCLC) (Colon-Otero G, et al. Cancer J Sci Am 1997;3:297-302) leading to a phase II trial of this regimen, the results of which are reported here. A total of 34 patients with stage IIIB or IV measurable or evaluable NSCLC were entered in this North Central Cancer Treatment Group phase II study. Treatment consisted of edatrexate 100 mg/m2 intravenously on day 1 and cisplatin 30 mg/m2/d on day 1 and day 2 followed by vinblastine 3 mg/m2 intravenously and doxorubicin 30 mg/m2 intravenously on day 2. Filgrastim was given at 300 microg subcutaneously daily from day 4 to day 18 or until an absolute neutrophil count of 2,000/mm3 or more was obtained. Cycles were repeated every 21 days until either progression or the development of intolerable toxicity. Sixteen of 34 evaluable patients responded to therapy, for a response rate of 47.1% with a 95% CI of 30.3% to 63.8%. Median time to disease progression was 132 days, median survival time was 219 days, and the estimated 1-year survival was 41.2% (95% CI of 27.6-61.5%). The EVAC/G-CSF regimen has significant antineoplastic activity as seen by the response rates for patients with NSCLC. However, this study had significant myelosuppressive toxicity; 56% patients had grade III or higher leukopenia with three treatment-related deaths observed. In addition, Quality of Life assessments indicate that patients experienced an overall decline in quality of life during the course of treatment. These mitigating factors need to be considered regarding further evaluation of this regimen in this patient population.

Trial of a topically administered local anesthetic (EMLA cream) for pain relief during central venous port accesses in children with cancer.

Procedure-related pain is a significant problem for many children receiving cytotoxic chemotherapy. In an effort to lessen this toxicity, we studied the efficacy and safety of administering topical local anesthesia using EMLA cream in 47 evaluable children with cancer undergoing implanted central venous port injections. Children (< 21 years old) scheduled to undergo repeated venous access procedures were selected for study. A placebo-controlled, randomized, double-blind, crossover study design was utilized. Statistically significant decreases in pain intensity scores (P < 0.002) were recorded by both children and investigators during the use of EMLA cream as compared with placebo. There was a good correlation between pain scores recorded by both patients and health care providers using both visual analog scales and categorized pain measurement tools. The topical application of EMLA cream 5% provides highly effective superficial anesthesia, and promises to be extremely useful for pain relief during percutaneous access procedures in cancer patients.

Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m2 by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol.

Treatment of acute nonlymphocytic leukemia in the elderly with intermediate high-dose cytosine arabinoside.

Effective treatment of the elderly patients (greater than or equal to 65 years) with acute nonlymphocytic leukemia (ANLL) remains elusive and controversial. In the present study, single-agent Cytosine Arabinoside (ARA-C) was administered at an intermediate dose level (500 mg/m2 intravenously [I.V.] 1-hour infusion q12 hours for 12 doses) to 30 newly diagnosed and previously untreated patients. Complete remission was achieved in seven patients after the initial cycle of treatment, in two patients after retreatment, and in one patient after delayed recovery of his peripheral count over a 6-month period. The toxicity of this schedule was primarily hematologic, and the response rate was in keeping with that reported by other groups using aggressive multiagent regimens.