A prospective surveillance model for rehabilitation for women with breast cancer

Background: The current model of care for breast cancer is focused on disease treatment followed by ongoing recurrence surveillance. This approach lacks attention to the patients’ physical and functional well-being. Breast cancer treatment sequelae can lead to physical impairments and functional limitations. Common impairments include pain, fatigue, upper extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis. Evidence supports prospective surveillance for early identification and treatment as a means to prevent or mitigate many of these concerns. Purpose: This paper proposes a prospective surveillance model for physical rehabilitation and exercise that can be integrated with disease treatment to create a more comprehensive approach to survivorship health care. The goals of the model are to promote surveillance for common physical impairments and functional limitations associated with breast cancer treatment, to provide education to facilitate early identification of impairments, to introduce rehabilitation and exercise intervention when physical impairments are identified and to promote and support physical activity and exercise behaviors through the trajectory of disease treatment and survivorship. Methods: The model is the result of a multi-disciplinary meeting of research and clinical experts in breast cancer survivorship and representatives of relevant professional and advocacy organizations. Outcomes: The proposed model identifies time points during breast cancer care for assessment of and education about physical impairments. Ultimately, implementation of the model may influence incidence and severity of breast cancer treatment related physical impairments. As such, the model seeks to optimize function during and following treatment and positively influence a growing survivorship community.

Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer

Purpose: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. Patients and Methods: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. Results: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. Conclusion: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC. © 2005 by American Society of Clinical Oncology.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis

Objective. Twelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis. Methods. One hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espirito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis. Results. Ectopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty-two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal-dominant monogenic disease. The mean age at which symptoms developed was 38 years. Conclusion. These families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.