BACKGROUND Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). RESULTS The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 non-hematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). CONCLUSIONS Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.)

Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.

This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.

Background: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseedsupplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and

BackgroundCALGB 100104 (Alliance) studied lenalidomide vs. placebo following autologous stem cell transplant (ASCT) for newly diagnosed myeloma patients, demonstrating improved time to progression (TTP) and overall survival (OS), and an increase in second primary malignancies (SPM) for lenalidomide at 34-months median follow-up. Here we report an updated intent-to-treat analysis at 91-months median follow-up.MethodsPatients were eligible if they had active myeloma, had received at most two induction regimens and had achieved stable disease or better in the first 100 days after ASCT. In this phase 3 study, 460 patients were randomised in a double-blind manner to either lenalidomide (n=231) or placebo (n=229) utilizing a permutated-block randomisation with fixed block size. Randomisation was stratified by three factors: normal or elevated β2-microglobulin level at registration (≤2·5 mg/L vs > 2·5 mg/L), prior use or nonuse of thalidomide during induction therapy, and prior use or nonuse of lenalidomide during induction therapy. The starting dose was 10 mg daily, escalated to 15 mg daily after three months. The primary endpoint was TTP (time of progressive disease or death from any cause) using intent-to-treat analysis. After three interim analyses, the study was unblinded at median follow-up of 18 months and 86/128 placebo patients without progressive disease chose to cross over to lenalidomide. This study is registered with ClinicalTrials.gov identifier NCT00114101; new patients are no longer being recruited, but some patients remain on treatment and in follow-up.FindingsThe median TTP for lenalidomide is 57·3 months (95% CI 44·2–73·3) and 28·9 months (95% CI 23·0–36·3) for placebo (hazard ratio (HR): 0·57, 95% CI 0·46–0·71, p<0·0001). The TTP benefit with lenalidomide was observed regardless of whether patients were in a complete response at time of randomisation or whether they had received thalidomide or lenalidomide induction therapy. The most common grade 3–4 adverse events were neutropenia (116 (50%) of 231 patients in the lenalidomide arm and 37 (16%) of 229 patients in the placebo arm) and thrombocytopenia (34 patients (15%) in the lenalidomide arm and 11 patients (4·8%) in the placebo arm. Eighteen haematological (7·8%) and 14 solid tumour (6·1%) SPMs have been diagnosed following randomisation and prior to disease progression in the lenalidomide arm vs. three haematological (1·3%) and nine solid tumour (3·9%) SPMs in the placebo arm. Of the placebo SPMs, three haematological and five of nine solid tumour SPMs were in the crossover subgroup.InterpretationDespite an increase in haematological adverse events and SPMs, lenalidomide maintenance therapy following ASCT significantly improves TTP and can be considered a standard of care.

In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar alone (n = 377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n = 564) have been compared in Parkinsonian patients. In patients who lost their response to conventional Madopar therapy the addition of l-deprenyl resulted in a significant recouping of levodopa effect. The survival analysis revealed a significant increase of life expectancy in Madopar--l-deprenyl group regardless of the fact whether or not the significant demographic differences between the two groups were taken into account. Although the mechanism underlying this action of l-deprenyl is not known, the results are interpreted as indicating l-deprenyl's ability to prevent or retard the degeneration of striatal dopaminergic neurons. l-Deprenyl is the first anti-Parkinson drug having such a property. This hypothesis is not far fetched since l-deprenyl selectively prevents the degeneration of striatal dopaminergic neurons induced in animals by the illicit drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since latter compound is known to cause Parkinsonism in man and primates or Parkinson-like neurochemical and pathological changes in other animals the implications of the present study involving monoamine oxidase activity and l-deprenyl are apparent.

Weight gain, a common side effect among breast cancer patients receiving adjuvant chemotherapy, may decrease quality of life and impair survival. Weight gain during treatment is a well-known problem and has been studied by many investigators. However, few controlled studies have been conducted to determine reasons to explain this apparent energy imbalance. An exploratory study was undertaken to quantitate potential changes in energy intake and specific components of energy expenditure in breast cancer patients receiving adjuvant chemotherapy. The research hypothesis was that a reduction in resting metabolic rate (RMR) would be observed during the period in which women received adjuvant chemotherapy. Twenty premenopausal patients with stage I or II breast cancer and receiving cyclophosphamide+doxorubicin+5-fluorouracil; cyclophosphamide +methotrexate+5-fluorouracil+/-doxorubicin; doxorubicin +cyclophosphamide+/-leucovorin; or methotrexate+5-fluorouracil +leucovorin chemotherapy were recruited. RMR, diet-induced thermogenesis, energy intake, physical activity, and body composition were assessed before the initiation and throughout the course of therapy. Complete data on 18 subjects suggest that RMR decreased significantly from baseline to midtreatment (P = 0.02) and rebounded to levels similar to those at baseline on completion of chemotherapy. Overall, levels of physical activity and energy intake also decreased significantly during treatment compared with baseline levels (P = 0.04 and P = 0.03, respectively). These findings suggest that chemotherapy provokes many significant changes in body composition and metabolic requirements. Additional research in this area will provide valuable insight into creating optimal interventions to curb weight gain in women with breast cancer.