Trimetrexate in untreated and previously treated patients with metastatic breast cancer: a Cancer and Leukemia Group B study

Twenty-two patients with previously untreated metastatic breast cancer and nineteen patients with refractory metastatic breast cancer were treated with trimetrexate (TMTX). Patients received TMTX 8 mg/m^2/day if previously treated or 12 mg/m^2/day if previously untreated, both given by intravenous bolus days 1-5, every 21 days. None of the patients previously treated for metastatic disease responded to TMTX. There was one partial responder among the22 patients with previously untreated metastatic disease. The primary toxicity was hematologic and occurred more frequently in patients with a pleural effusion, low serum protein or albumin, or poor performance status. There were three toxic deaths. The study for previously untreated patients required cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) after 4 cycles of TMTX. This study design for previously untreated patients allows the Cancer and Leukemia Group B (CALGB) to prospectively evaluate the activity of new agents in “chemotherapy-sensitive” metastatic breast cancer

Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing �-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2 % of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means Received 10/26/98; revised 2/8/99; accepted 3/11/99. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

Once Daily High-dose Radiation (≥60 Gy) Treatment in Limited Stage Small Cell Lung Cancer.

BACKGROUND: To investigate outcomes and prognostic factors in patients treated with once daily high-dose (≥60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy. METHODS: We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005-2013. Patients treated with HDRT (≥60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI). RESULTS: 42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30-62%) and 21% (CI=7-38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p CONCLUSIONS: In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported by Turris

Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies.

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients

SBRT to adrenal metastases provides high local control with minimal toxicity

Purpose: The adrenal glands are a common site of metastases because of their rich blood supply. Previously, adrenal metastases were treated with systemic chemotherapy or, more rarely, with surgical resection or palliative radiation therapy. Stereotactic body radiation therapy (SBRT) has recently emerged as an attractive noninvasive approach to definitively treat these lesions. We present our experience in treating adrenal metastases using SBRT and review the current literature. Methods and materials: This is a single-institution retrospective review of patients who received SBRT to adrenal metastases originating from various primary malignancies. Patients who were eligible for SBRT included those with limited metastatic disease (≤5 sites) with otherwise controlled metastatic disease and uncontrolled adrenal metastases. Results: Ten patients met the study's inclusion criteria and received SBRT doses of 30 to 48 Gy in 3 to 5 fractions. Acute sequelae of SBRT treatment included 4 patients with grades 1 or 2 nausea, 3 patients with grade 1 fatigue, and 1 with grade 1 diarrhea. The median follow-up was 6 months with a median overall survival of 9.9 months. One patient demonstrated progressive adrenal gland disease 18.8 months after SBRT treatment. Seven patients developed new distant metastases after treatment, with a median progression-free survival of 3.4 months. Three months after SBRT to the adrenal gland, 1 patient developed a gastrointestinal bleed. Conclusions: These results complement the limited existing body of literature by demonstrating that SBRT provides good control of treated adrenal gland metastasis; however, high-grade late toxicities may occur. More stringent dose constraint limits may prevent associated serious adverse events