Ivy Altomare

Patient-Oncologist Cost Communication, Financial Distress, and Medication Adherence

BACKGROUND Little is known about the association between patient-oncologist discussion of cancer treatment out-of-pocket (OOP) cost and medication adherence, a critical component of quality cancer care. METHODS We surveyed insured adults receiving anticancer therapy. Patients were asked if they had discussed OOP cost with their oncologist. Medication nonadherence was defined as skipping doses or taking less medication than prescribed to make prescriptions last longer, or not filling prescriptions because of cost. Multivariable analysis assessed the association between nonadherence and cost discussions. RESULTS Among 300 respondents (86% response), 16% (n = 49) reported high or overwhelming financial distress. Nineteen percent (n = 56) reported talking to their oncologist about cost. Twenty-seven percent (n = 77) reported medication nonadherence. To make a prescription last longer, 14% (n = 42) skipped medication doses, and 11% (n = 33) took less medication than prescribed; 22% (n = 66) did not fill a prescription because of cost. Five percent (n = 14) reported chemotherapy nonadherence. To make a prescription last longer, 1% (n = 3) skipped chemotherapy doses, and 2% (n = 5) took less chemotherapy; 3% (n = 10) did not fill a chemotherapy prescription because of cost. In adjusted analyses, cost discussion (odds ratio [OR] = 2.58; 95% CI, 1.14 to 5.85; P = .02), financial distress (OR = 1.64, 95% CI, 1.38 to 1.96; P < .001) and higher financial burden than expected (OR = 2.89; 95% CI, 1.41 to 5.89; P < .01) were associated with increased odds of nonadherence. CONCLUSION Patient-oncologist cost communication and financial distress were associated with medication nonadherence, suggesting that cost discussions are important for patients forced to make cost-related behavior alterations. Future research should examine the timing, content, and quality of cost-discussions.

Retrovirally transduced human dendritic cells can generate T cells recognizing multiple MHC class I and class II epitopes from the melanoma antigen glycoprotein 100

Involvement of tumor-Ag specific CD4+ and CD8+ T cells could be critical in the generation of an effective immunotherapy for cancer. In an attempt to optimize the T cell response against defined tumor Ags, we previously developed a method allowing transgene expression in human dendritic cells (DCs) using retroviral vectors. One advantage of using gene-modified DCs is the potential ability to generate CD8+ T cells against multiple class I-restricted epitopes within the Ag, thereby eliciting a broad antitumor immune response. To test this, we generated tumor-reactive CD8+ T cells with DCs transduced with the melanoma Ag gp100, for which a number of HLA-A2-restricted epitopes have been described. Using gp100-transduced DCs, we were indeed able to raise T cells recognizing three distinct HLA-A2 epitopes within the Ag, gp100154–162, gp100209–217, and gp100280–288. We next tested the ability of transduced DCs to raise class II-restricted CD4+ T cells. Interestingly, stimulation with gp100-transduced DCs resulted in the generation of CD4+ T cells specific for a novel HLA-DRβ1*0701-restricted epitope of gp100. The minimal determinant of this epitope was defined as gp100174–190 (TGRAMLGTHTMEVTVYH). These observations suggest that retrovirally transduced DCs have the capacity to present multiple MHC class I- and class II-restricted peptides derived from a tumor Ag, thereby eliciting a robust immune response against that Ag.

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

PURPOSE For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC. METHODS Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily. RESULTS Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1-2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%). CONCLUSIONS Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.

A Phase II Study of Capecitabine, Oxaliplatin, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

BACKGROUND Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. METHODS Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m(2) BID on days 1-14, and oxaliplatin 130 mg/m(2) with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor. RESULTS Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome. CONCLUSIONS Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer.

The 5, 10 methylenetetrahydrofolate reductase C677T mutation and risk of fetal loss: a case series and review of the literature

BackgroundThe true relationship between methylenetetrahydrofolate reductase C677T homozygosity and risk of recurrent spontaneous abortion is unknown, and it is unclear if women with these mutations should be anticoagulated during pregnancy.ObjectivesWe report a series of 8 patients with this issue and review the current literature.Methods8 patients (3 of whom were actively pregnant) were referred with histories of spontaneous fetal loss; hypercoaguability work-ups revealed each were homozygous for the MTHFR C677T mutation without other thrombophilias.ResultsIn the 3 women who have conceived, treatment with LMW heparin during pregnancy led to two full-term births and one additional pregnancy without complication. For the 5 who have not, we recommended treatment with LMW heparin upon conception.ConclusionWe provide evidence to support the relationship between MTHFR C677T mutations and recurrent fetal loss, and to suggest that anticoagulation of these patients during pregnancy can lead to a successful pregnancy outcome.

Everolimus in colorectal cancer

Introduction: There has been a strong preclinical rationale for studying mammalian target of rapamycin (mTOR) inhibitors as single agents or in combination, in multiple malignancies and colorectal cancer in particular. Areas covered: The authors summarize the complete clinical experience to date of all trials, both published and in abstract form, of everolimus in colorectal cancer. While initial Phase I trials showed promise, further studies have confirmed that single agent everolimus is not active in advanced metastatic colorectal carcinoma with trials showing single agent tolerability, but without significant hints of efficacy in terms of either objective tumor responses or prolonged stable disease. Combination regimens, including combinations with cytotoxic chemotherapy, and inhibitors of VEGF, EGFR and HDAC have been tested specifically in the colorectal setting in Phase I and Phase II clinical trials. The authors discuss the potential reasons for mixed results and suggest future directions for the development of everolimus in colorectal malignancies. Expert opinion: Studies demonstrate limited clinical activity of everolimus for the treatment of advanced colorectal cancer and have been complicated by increases in toxicity. However, the central role of the PI3K/mTOR pathway in cancer biology suggests that other drug combinations with mTOR inhibition may still merit evaluation.

Out-of-Pocket Costs, Financial Distress, and Underinsurance in Cancer Care

This cross-sectional survey study examines financial distress and cost expectations among patients with cancer presenting for anticancer therapy.

Bleeding and mortality outcomes in ITP clinical trials: A review of thrombopoietin mimetics data

Patients with ITP may have severe thrombocytopenia, putting them at risk for serious bleeding. ITP trials of new treatments must allow use of standard‐of‐care therapies to prevent serious bleeding. Thrombopoietin mimetic trials used platelet counts and rescue/concomitant medication use as endpoints. These trials were of insufficient size and duration to measure mortality or serious bleeding, which are infrequent with appropriate treatment. A recent Cochrane review criticized the thrombopoietin mimetic registrational trials for inadequately assessing bleeding and survival. We discuss how these endpoints are difficult to measure in clinical trials designed to improve platelet counts and minimize bleeding, in accordance with ethical trial design. Am. J. Hematol. 2012.

ReCAP: Physician Experience and Attitudes Toward Addressing the Cost of Cancer Care

PURPOSE We surveyed US cancer doctors to examine current attitudes toward cost discussions and how they influence decision making and practice management. METHODS We conducted a self-administered, anonymous, electronic survey of randomly selected physician ASCO members to evaluate the frequency and nature of cost discussions reported by physicians, attitudes toward discussions of cost in clinics, and potential barriers. RESULTS A total of 333 of 2,290 physicians responded (response rate [RR], 15%; adjusted RR after omitting nonpracticing physician ASCO members, 25%), Respondent practice settings were 45% academic and 55% community/private practice. Overall, 60% reported addressing costs frequently/always in clinic, whereas 40% addressed costs rarely/never. The largest reported barrier was lack of resources to guide discussions. Those who reported frequent discussions were significantly more likely to prioritize treatments in terms of cost and believed doctors should explain patient and societal costs. A total of 36%did not believe that doctors should discuss costs with patients. Academic practitioners were significantly less likely to discuss costs (odds ratio [OR], 0.41; P = .001) and felt less prepared for such discussions (OR, 0.492; P = .005) but were more likely to consider costs to the patient (OR, 2.68; P = .02) and society (OR, 1.822; P = .02). CONCLUSION Although the majority of respondents believe it is important to consider out-of-pocket costs to patients, a substantial proportion do not discuss or consider costs of cancer care. Lack of consensus on the importance of such discussions and uncertainty regarding the optimal timing and content appear to be barriers to addressing costs of care with patients.

The Neoadjuvant Treatment of Rectal Cancer: A Review

Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer, especially in the curative setting. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. We review both pivotal trial data that has shaped the current standard of care, fluoropyrimidine-based chemoradiotherapy, while also presenting results from more recent studies, which aim to outperform this standard. Strategies combining 5FU radiotherapy with oxaliplatin, VEGF inhibition, EGFR inhibition, other targeted agents, and/or use of induction chemotherapy hold promise but thus far have failed to improve outcomes in randomized trials. Results of studies such as the ongoing PROSPECT trial may help further define our current therapeutic algorithm for stage II and III rectal cancer.