Peter Kirkbride

Dexamethasone for the Prophylaxis of Radiation-Induced Emesis: A National Cancer Institute of Canada Clinical Trials Group Phase III Study

PURPOSE To investigate the efficacy of dexamethasone as a prophylactic antiemetic for patients receiving fractionated radiotherapy to the upper abdomen in a randomized controlled trial. PATIENTS AND METHODS One hundred fifty-four patients planned to receive fractionated radiotherapy to fields involving the upper abdomen (minimum total dose, 20 Gy; minimum number of fractions, five) were randomized to receive prophylactic dexamethasone (2 mg orally three times a day [tid], starting in the morning of first treatment and continuing until after their fifth treatment) or placebo. The primary end point of the study was the proportion of patients free from emesis during the study period. Secondary end points included a quality-of-life assessment using the core questionnaire of the European Organization for Research and Treatment of Cancer and side effects of dexamethasone therapy in this population of patients. RESULTS Fifty-four (70%) out of 75 patients receiving dexamethasone had complete protection versus 37 (49%) out of 75 patients on placebo (P = .025). Most emetic episodes occurred during the initial phase of treatment. Although there was no difference in global quality of life between the two sets of patients, patients receiving dexamethasone had less nausea and vomiting and less loss of appetite but more insomnia. CONCLUSION Dexamethasone 2 mg tid seems to be an effective prophylactic antiemetic in this situation. Side effects were acceptable, but there seemed to be no overall effect on global quality of life.

Randomized Trial of High-Dose Chemotherapy With Autologous Peripheral-Blood Stem-Cell Support Compared With Standard-Dose Chemotherapy in Women With Metastatic Breast Cancer: NCIC MA.16

PURPOSE We conducted a multicenter, randomized trial to compare progression-free survival (PFS), overall survival (OS), and quality of life in women with metastatic breast cancer (MBC) receiving high-dose chemotherapy plus autologous stem-cell transplantation (ASCT; HDCT) compared with standard-dose therapy. PATIENT AND METHODS Between April 1997 and December 2000, 386 women with MBC and no prior chemotherapy for metastatic disease were registered. After initial response to anthracycline- or taxane-based induction chemotherapy, 224 patients were randomly assigned: 112 to high-dose cyclophosphamide, mitoxantrone, and carboplatin chemotherapy and ASCT (HDCT), and 112 to standard therapy (ST). Median age was 47 years (range, 25 to 67 years). Thirty two percent of women randomly assigned had estrogen and progesterone receptor-negative breast cancer, 42% had visceral metastases, and 58% had bone metastases. Complete remission rates before random assignment were 11% for those receiving HDCT and 12% for those receiving ST. RESULTS After a median follow-up of 48 months, 79 deaths were observed in the HDCT arm and 77 deaths were observed in the ST arm; seven patients (6%) in the HDCT arm died as a result of toxicity. The median OS was 24 months for the HDCT arm (95% CI, 21 to 35 months) and 28 months for ST (95% CI, 22 to 33 months; hazard ratio [HR], 0.9; 95% CI, 0.6 to 1.2; P = .43). PFS was 11 months for HDCT and 9 months for ST (HR, 0.6 in favor of HDCT; 95% CI, 0.5 to 0.9; P = .006). CONCLUSION HDCT did not improve OS in women with MBC when used as consolidation after response to induction chemotherapy.

Outcome of curative management of malignant tumours of the parotid gland.

PURPOSE The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed. MATERIALS AND METHODS A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour. RESULTS All patients were initially managed with a parotidectomy, and postoperative x-ray radiation therapy (XRT) was administered to 159 patients. The actuarial 5-year cause-specific survival and locoregional control rates were 76% and 81%, respectively. The survival and locoregional control rates for patients treated with surgery alone versus surgery plus postoperative XRT were not statistically different. A multiple regression analysis identified only age and tumour category to be independently significant prognostic factors for both survival and locoregional control. CONCLUSION We would recommend that patients with malignant parotid gland tumours be managed with parotidectomy, followed by postoperative XRT for tumours with residual disease, aggressive histology, and/or positive lymph nodes.

Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

PURPOSE The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. PATIENTS AND METHODS A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer-specific checklist or the Functional Assessment of Cancer Therapy-Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. RESULTS Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy-Prostate total score, treatment outcome index, and physical and functional well-being. CONCLUSION The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL.

A phase I/II study of paclitaxel (Taxol®) and concurrent radiotherapy in advanced nonsmall cell lung cancer

PURPOSE The addition of chemotherapy to radical radiotherapy (XRT) has been shown to improve survival in locally advanced nonsmall cell lung cancer (9). Consequently, different chemotherapeutic regimens in combination with XRT are being evaluated in the treatment of this disease. Paclitaxel (TAXOL) may be a valuable drug in this situation as, in addition to a demonstrated activity in NSCLC, it has been shown to enhance the effect of radiation on cell lines in vitro. METHODS AND MATERIALS Seventeen patients were enrolled onto a Phase I/II trial to determine the maximum tolerated dose of paclitaxel given by a 3-h infusion every 2 weeks throughout a 6-week course of XRT, 60 Gy in 30 daily fractions, in patients with Stage III NSCLC and then to describe the response rate of this combination in an expanded cohort of patients treated at the recommended phase II dose. Three patients were entered at each dose level (45, 90, 120, and 135 mg/m2), except for the 120 mg/m2 dose level, which was expanded to nine patients. RESULTS The dose limiting toxicity was neutropenia--two of three patients treated at the 135 mg/m2 level experienced Grade 3 neutropenia on day 15, which precluded administration of scheduled chemotherapy. Esophagitis was mild to moderate, and although profound lymphopenia was observed at all dose levels, there was no evidence of associated opportunistic infections. Of the nine patients treated at the recommended Phase II dose of 120 mg/m2, there were one complete and six partial responses (response rate 78%). CONCLUSION The combination of XRT, 60 Gy in 6 weeks and paclitaxel, 120 mg/m2 q 2 weeks, can be safely given to patients with NSCLC, and although it demonstrates activity in this situation, consideration should be given to the addition of other agents, such as platinum compounds.