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BACKGROUND: IGF signaling has been implicated in the pathogenesis and progression of ovarian carcinoma (OC). Single agent activity and safety of ganitumab (AMG 479), a fully human monoclonal antibody against IGF1R that blocks binding of IGF1 and IGF2, were evaluated in patients with platinum-sensitive recurrent OC. METHODS: Patients with CA125 progression (GCIG criteria) or measurable disease per RECIST following primary platinum-based therapy received 18 mg/kg of ganitumab q3w. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 by an independent radiology review committee (IRC) and/or GCIG CA125 criteria. Secondary endpoints included clinical benefit rate (CBR), progression free survival (PFS) and overall survival (OS). RESULTS: 61 pts. were accrued. Objective responses were seen in 5/61 patients (ORR 8.2%, 95% CI, 3.1-18.8) with 1 partial response (PR) by RECIST and 2 complete responses (CR) as well as 2 PR by CA125 criteria. CBR was 80.3% (95% CI, 67.8-89.0%). The median PFS according to RECIST by IRC was 2.1 months (95% CI, 2.0-3.1). The median PFS per RECIST IRC and/or CA125 was 2.0 months (95% CI, 1.8-2.2). The median OS was 21 months (95% CI, 19.5-NA). The most common overall adverse events were fatigue (36.1%) and hypertension (34.4%). Grade 1/2 hyperglycemia occurred in 30.4% of patients. Hypertension (11.5%) and hypersensitivity (8.2%) were the most frequent grade 3 adverse events. CONCLUSIONS: IGF1R inhibition with ganitumab was well-tolerated, however, our results do not support further study of ganitumab as a single agent in unselected OC patients.

BackgroundCancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events.MethodsThis meta-analysis included studies from the 2006 Cochrane meta-analysis, studies published/updated since the 2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of cancer. Data were summarised using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsResults indicated that ESA use did not significantly affect mortality (60 studies: OR=1.06; 95% CI: 0.97-1.15) or disease progression (26 studies: OR=1.01; 95% CI: 0.90-1.14), but increased the risk for venous-thromoboembolic events (44 studies: OR=1.48; 95% CI: 1.28-1.72).ConclusionThough this meta-analysis showed no significant effect of ESAs on survival or disease progression, prospectively designed, future randomised clinical trials will further examine the safety and efficacy of ESAs when used according to the revised labelling information.

John A Glaspy,1 Michelle Z Lim-Watson,2 Michael A Libre,3 Swagata S Karkare,3 Nandini Hadker,3 Aleksandra Bajic-Lucas,2 William E Strauss,2 Naomi V Dahl2 1UCLA School of Medicine, Los Angeles, CA, USA; 2AMAG Pharmaceuticals, Inc., Waltham, MA, USA; 3Trinity LifeSciences, Waltham, MA, USACorrespondence: Naomi V DahlAMAG Pharmaceuticals, Inc., 1100 Winter Street, Waltham, MA 02451, USATel +1 617-498-7650Email ndahl@amagpharma.comBackground: Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia.Objective: The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US).Methods: A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs.Results: The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as “asymptomatic” or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities.Conclusion: Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.Keywords: IDA, phosphate, hypophosphatemia, iron supplementation

Context: High-dose chemotherapy poses considerable challenges to emesis management. Although prior studies suggest that acupuncture may reduce nausea and emesis, it is unclear whether such benefit comes from the nonspecific effects of attention and clinician-patient interaction.Objective: To compare the effectiveness of electroacupuncture vs minimal needling and mock electrical stimulation or antiemetic medications alone in controlling emesis among patients undergoing a highly emetogenic chemotherapy regimen.Design: Three-arm, parallel-group, randomized controlled trial conducted from March 1996 to December 1997, with a 5-day study period and a 9-day follow-up.Setting: Oncology center at a university medical center.Patients: One hundred four women (mean age, 46 years) with high-risk breast cancer.Interventions: Patients were randomly assigned to receive low-frequency electroacupuncture at classic antiemetic acupuncture points once daily for 5 days (n = 37); minimal needling at control points with mock electrostimulation on the same schedule (n = 33); or no adjunct needling (n = 34). All patients received concurrent triple antiemetic pharmacotherapy and high-dose chemotherapy (cyclophosphamide, cisplatin, and carmustine).Main Outcome Measures: Total number of emesis episodes occurring during the 5-day study period and the proportion of emesis-free days, compared among the 3 groups.Results: The number of emesis episodes occurring during the 5 days was lower for patients receiving electroacupuncture compared with those receiving minimal needling or pharmacotherapy alone (median number of episodes, 5, 10, and 15, respectively; P<.001). The electroacupuncture group had fewer episodes of emesis than the minimal needling group (P<.001), whereas the minimal needling group had fewer episodes of emesis than the antiemetic pharmacotherapy alone group (P =.01). The differences among groups were not significant during the 9-day follow-up period (P =.18).Conclusions: In this study of patients with breast cancer receiving high-dose chemotherapy, adjunct electroacupuncture was more effective in controlling emesis than minimal needling or antiemetic pharmacotherapy alone, although the observed effect had limited duration. JAMA. 2000;284:2755-2761. [ABSTRACT FROM AUTHOR]