As many breast cancer patients receive adjuvant chemotherapy using anthracyclines or anthracenediones and taxanes, more therapeutic options are needed for subsequent lines of therapy. Pemetrexed (ALIMTA, multitargeted antifolate, LY231514) is a novel antifolate that inhibits several enzymes in the de novo pathways of pyrimidine and purine biosynthesis. This paper reports on a subset analysis of a phase II clinical trial of pemetrexed in heavily pretreated metastatic breast cancer (MBC) patients. Patients were required to have received prior first-line anthracycline therapy for metastatic disease. Prior adjuvant chemotherapy and prior taxanes were allowed. A substantial subset of the study population (31 of 72 patients, 43%) had also received a taxane in the metastatic setting. All patients were treated with pemetrexed, 600 mg/m2 by intravenous infusion, once every 21 days. In the study subset, 23 of 31 (74%) patients were anthracyclines failures (progression > 30 days following treatment), and eight (26%) patients were anthracyclines refractory (progression during or < or = 30 days of treatment). The median age was 55 years (range, 30-75 years) and the median World Health Organization performance status was 0. Metastases were present in the liver (61%), lung (29%), bone (6%), and soft tissue (19%). The overall response rate for this subset was 26%, with one complete response, seven partial responses, and 13 (42%) patients with stable disease. The median duration of response was 5.4 months and median survival was 12.8 months. Pemetrexed was well tolerated by patients in the study. This post hoc analysis suggests promising activity in MBC patients previously treated with both anthracyclines and taxanes. An ongoing trial is prospectively evaluating activity in this same population.

BACKGROUND

To clarify the implications and limitations of external beam radiation monotherapy for localized prostate cancer, the long-term outcomes and prognostic factors were investigated.

METHODS

Between 1976 and 1994, 91 patients with untreated prostate cancer were treated with external beam radiation therapy alone. Thirty-two were classified as T1b, eight were T2a, four were T2b and 47 were T3. Pelvic lymphadenectomy was carried out in 69 cases; 57 were staged as pN0, eight were pN1, four were pN2 and 22 were pNX. Linac X-rays were used in 55 cases, fast neutron in 15 and a combination of the two in 21. No other therapy was given until relapse and when relapse was evident endocrine therapy was started.

RESULTS

The observation period ranged from 3 to 206 months with a median of 78 months. Local control rate and disease-free, cause-specific and overall survivals at 10 years were 74.0, 49.6, 74.2 and 39.2%, respectively. By univariate analysis, T category, pN category and histologic grade were significant prognostic indicators for disease-free survival. Multivariate analysis revealed that T category was an independent prognostic factor. In T2b and T3 diseases, pN0/1 patients demonstrated significantly better disease-free survival than pNX.

CONCLUSIONS

A favorable long-term outcome was achieved by external beam radiation monotherapy in patients with minimally extended prostate cancer (T1b and T2a). For locally advanced disease (T2b and T3), staging pelvic lymphadenectomy would be useful for the selection of patients.