An economic analysis comparing health care resource use and cost of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin versus gemcitabine and cisplatin as neoadjuvant therapy for muscle invasive bladder cancer.

PURPOSE: To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). METHODS: Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis. RESULTS: 137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P < 0.001) and higher proportion of ECOG-PS = 0 (P < 0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P < 0.001), central line placement (P = 0.017), cardiac imaging (P < 0.001), and infusion visits (P < 0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P < 0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient. CONCLUSIONS: Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting.

PURPOSE: Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). METHODS: This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. RESULTS: 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). CONCLUSION: In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

Lanreotide vs octreotide LAR for patients with advanced gastroenteropancreatic neuroendocrine tumors: An observational time and motion analysis.

BACKGROUND: Lanreotide and octreotide acetate suspension for injectable (LAR) are both recommended for clinical use in patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. However, each agent possesses unique attributes in terms of their drug-delivery characteristics. The study objective was to compare overall drug-delivery efficiency between lanreotide and octreotide LAR in gastroenteropancreatic neuroendocrine tumor patients. METHODS: This study employed an observational time and motion design among patients treated with lanreotide or octreotide LAR across five US cancer centers. Baseline patient data collection included age, disease grade and duration, prior therapies and performance status. Drug-delivery time (drug preparation and administration), total patient time and resource use data were collected for gastroenteropancreatic neuroendocrine tumors receiving lanreotide (n = 22) or octreotide LAR (n = 22). Following each administration, qualitative data on the drug-delivery experience was collected from patients and nurses. RESULTS: Lanreotide was associated with a significant reduction in mean delivery time (2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4 to 7.9; p = 0.004). The mean total patient time for lanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6 minutes; p = 0.97). Nurses reported increased concerns with octreotide LAR related to needle clogging (p = 0.034) and device failures (p = 0.057). Overall, lanreotide had a median satisfaction score of 5.0 compared to a score of 4.0 with octreotide LAR (p = 0.03). CONCLUSIONS: Lanreotide was associated with significant reductions in drug-delivery time compared to octreotide LAR, which contributed to an improvement in overall healthcare efficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03017690.

Modeling the economic outcomes of immuno-oncology drugs: alternative model frameworks to capture clinical outcomes.

BACKGROUND: Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. MATERIALS AND METHODS: This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy. Two variants of the PSM and a Markov model were populated with data from one clinical trial in metastatic melanoma patients. Short-term modeled outcomes were benchmarked to the clinical trial data and a lifetime model horizon provided estimates of life years and quality adjusted life years (QALYs). RESULTS: The PSM-based models produced short-term outcomes closely matching the trial outcomes. Adding health states generated increased QALYs while providing a more granular representation of outcomes for decision making. The Markov model gave the greatest level of detail on outcomes but gave short-term results which diverged from those of the trial (overstating year 1 progression-free survival by around 60%). CONCLUSION: Increased sophistication in the representation of disease dynamics in economic models is desirable when attempting to model treatment response in I-O. However, the assumptions underlying different model structures and the availability of data for health state mapping may be important limiting factors.

The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting.

BACKGROUND: Despite the availability of effective antiemetics and evidence-based guidelines, up to 40% of cancer patients receiving chemotherapy fail to achieve complete nausea and vomiting control. In addition to type of chemotherapy, several patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) have been identified. To incorporate these factors into the optimal selection of prophylactic antiemetics, a repeated measures cycle-based model to predict the risk of ≥ grade 2 CINV (≥2 vomiting episodes or a decrease in oral intake due to nausea) from days 0 to 5 post-chemotherapy was developed. PATIENTS AND METHODS: Data from 1198 patients enrolled in one of the five non-interventional CINV prospective studies were pooled. Generalized estimating equations were used in a backwards elimination process with the P-value set at <0.05 to identify the relevant predictive factors. A risk scoring algorithm (range 0-32) was then derived from the final model coefficients. Finally, a receiver-operating characteristic curve (ROCC) analysis was done to measure the predictive accuracy of the scoring algorithm. RESULTS: Over 4197 chemotherapy cycles, 42.2% of patients experienced ≥grade 2 CINV. Eight risk factors were identified: patient age <60 years, the first two cycles of chemotherapy, anticipatory nausea and vomiting, history of morning sickness, hours of sleep the night before chemotherapy, CINV in the prior cycle, patient self-medication with non-prescribed treatments, and the use of platinum or anthracycline-based regimens. The ROC analysis indicated good predictive accuracy with an area-under-the-curve of 0.69 (95% CI: 0.67-0.70). Before to each cycle of therapy, patients with risk scores ≥16 units would be considered at high risk for developing ≥grade 2 CINV. CONCLUSIONS: The clinical application of this prediction tool will be an important source of individual patient risk information for the oncology clinician and may enhance patient care by optimizing the use of the antiemetics in a proactive manner.

A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer.

Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3 months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12 weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61 years (range 37-87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81 %) with zoledronic acid and 18/29 (62 %) with pamidronate (p = 0.095). Mean decrease in sCTx (mean difference between groups = 50 ng/L, 95 % CI 18-84; p = 0.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.

A comparison of toxicity and health care resource use between eribulin, capecitabine, gemcitabine, and vinorelbine in patients with metastatic breast cancer treated in a community oncology setting.

BACKGROUND: Capecitabine (C), gemcitabine (G), and vinorelbine (V) are commonly used as single agents in patients with metastatic breast cancer. Eribulin (E) is one of the most recent cytotoxic agents to gain regulatory approval for metastatic breast cancer in the United States as a single agent. EMBRACE - a large randomized trial demonstrated the safety and overall survival benefit of eribulin in heavily pretreated metastatic breast cancer patients compared to treatment of physician's choice. In this analysis, toxicity and the associated health care resource use were compared between the four agents in a sample of metastatic breast cancer patients treated in a US community oncology setting. METHODS: This study identified 411 patients (C=144, G=81, V=96, and E=90) who were treated in 19 community oncology clinics over the preceding two-year period. Data collection included baseline patient and disease characteristics, duration of therapy, use of supportive care drugs, type of dose limiting toxicities, and their impact on overall health care resource use. RESULTS: The median lines of therapy for C, G, V, and E were second, third, third, and fourth, respectively. Patients were comparable with respect to baseline comorbidities, performance status, serum creatinine, hemoglobin, neutrophil, and platelet counts. The proportion reporting at least one adverse event (any grade) with C, G, V, and E was 45%, 65%, 75%, and 63%. The most commonly reported toxicities (regardless of grade) for C, G, and V were diarrhea (19.4%), anemia (34.6%), and neutropenia (50.0%), respectively. The most common toxicity for E was neutropenia (32.2%). Overall, 5.6%, 19.8%, 22.9%, and 22.2% of patients receiving C, G, V, and E required at least one medical intervention to manage a toxic event. Toxicity was the cause of treatment discontinuation in 25.7%, 8.6%, 11.5%, and 8.9% of C, G, V, and E patients, respectively. The primary cause for treatment discontinuation in all four cohorts was disease progression. CONCLUSIONS: Eribulin demonstrated a comparable patient safety profile to gemcitabine and vinorelbine, even when administered after three lines of prior therapies. Capecitabine was generally used in earlier lines, had less neutropenia and anemia, but more treatment discontinuations due to toxicity.

What is a new drug worth? An innovative model for performance-based pricing.

This article focuses on a novel method to derive prices for new pharmaceuticals by making price a function of drug performance. We briefly review current models for determining price for a new product and discuss alternatives that have historically been favoured by various funding bodies. The progressive approach to drug pricing, proposed herein, may better address the views and concerns of multiple stakeholders in a developed healthcare system by acknowledging and incorporating input from disparate parties via comprehensive and successive negotiation stages. In proposing a valid construct for performance-based pricing, the following model seeks to achieve several crucial objectives: earlier and wider access to new treatments; improved transparency in drug pricing; multi-stakeholder involvement through phased pricing negotiations; recognition of innovative product performance and latent changes in value; an earlier and more predictable return for developers without sacrificing total return on investment (ROI); more involved and informed risk sharing by the end-user.

Management of patients with Cushing's disease: a Canadian cost of illness analysis.

BACKGROUND: Cushing's disease (CD) is a rare disorder caused by increased pituitary secretion of adrenocorticotropic hormone (ACTH) resulting in elevated production of cortisol. It is associated with multiple adverse cardiovascular, metabolic, musculoskeletal and mental consequences. Patients with CD require substantial health care resources both in terms of treatments with a curative intent and control of disease related co-morbidities. In this study, a cost of illness analysis was conducted to estimate the direct cost of CD care in Canada. METHODS: This was a retrospective cohort study of 86 CD patients. Data collection included patient demographic and disease related information, existing comorbidities, treatments received and all clinical outcomes. In addition, healthcare resource utilization to manage CD was also collected. Once the mean cost per patient was determined, the overall disease prevalence was used to estimate the total direct cost of illness in Canada. RESULTS: The sample included 86 CD patients, with a mean age of 43 years at diagnosis, 72% were female. All received a first line intervention consisting of transsphenoidal pituitary surgery (78%), bilateral adrenalectomy (5%), radiation therapy (5%) or medical therapy ± radiation (13%). In addition, 18 and 14 patients subsequently received a second and third line intervention, respectively. The mean cost was $85,946 per patient over the first three lines of therapy. Combining this estimate with the reported disease prevalence (5.5 patients per 100,000 [95%CI: 4.2 to 6.8]), the total direct cost of CD in Canada was estimated to be approximately $80.6 million (95%CI: $61.5 to $99.6 million) over the first 3 lines of therapy. CONCLUSIONS: CD is a debilitating condition that is associated with substantial health care costs. Strategies that provide clinical cure or long term disease control need to be identified to reduce patient morbidity and to save health care costs in patients who remain uncontrolled.

Preference weights for chemotherapy side effects from the perspective of women with breast cancer.

Perceptions among women with breast cancer about the relative importance of different potential chemotherapy side effects is not well understood. A survey was performed by women receiving chemotherapy for breast cancer. Grade I/II (mild to moderate) and III/IV (moderate to severe) descriptions of nine common chemotherapy side effects were assigned preference weights using the standard gamble technique. For each hypothetical side effect, patients could choose to stay in the respective side effect state or take a gamble between full health (probability p) or being dead (1 - p). For each side effect, p was varied until the patient was indifferent between these options. The survey also included questions about the importance of survival, slowing cancer growth, and quality of life. This analysis included 69 patients; mean age 54 years (range 35-84), representing all cancer stages. Standard gamble preferences were lowest (i.e., least preferred) for grade III/IV nausea/vomiting (0.621), indicating that patients would, on average, risk a 38 % chance of being dead to avoid having grade III/IV nausea/vomiting for the rest of their lives. The next least preferred side effects were grade III/IV diarrhea (0.677) and grade III/IV sensory neuropathy (0.694). Survival appeared more important than slowing cancer growth and maintaining quality of life across cancer stages. Nevertheless, patients with advanced disease placed less importance on survival (p = 0.09) and higher importance on quality of life (p = 0.05). These standard gamble utilities provide unique insights into chemotherapy toxicities from the patient perspective. Differences in the relative importance of overall survival and quality of life with treatment existed between patients with different stages of disease. These studies should be expanded as the data may also be used to calculate quality-adjusted life expectancy in cost-effectiveness evaluations of breast cancer chemotherapies.

Clinical outcomes of women with metastatic breast cancer treated with nab-paclitaxel: experience from a single academic cancer centre.

BACKGROUND: Nab-paclitaxel is a solvent-free, taxane-based chemotherapy approved for the treatment of metastatic breast cancer (mbc). This study reports clinical benefit and toxicities experienced by women with mbc treated with nab-paclitaxel at the Ottawa Hospital Cancer Centre. METHODS: Women with mbc treated with single-agent nab-paclitaxel between June 2006 and December 2010 were included in this analysis. Retrospective data obtained included demographics, disease characteristics, prior chemotherapy, nab-paclitaxel treatment, toxicity, and survival. Clinical benefit was defined as partial or complete response or stable disease (by clinical or radiologic evaluation, or both) at 6 months or more. RESULTS: Of 43 women (mean age: 57.0 years; range: 34-74 years), most had disease positive for estrogen or progesterone receptor (72.1%, 58.1%), or both. Nab-paclitaxel was administered weekly (qw: 44.2%), every 3 weeks (q3w: 46.5%), q3w switched to qw (7.0%), or qw switched to q3w (2.3%). Median duration of therapy was 5.1 months (qw) and 3.0 months (q3w). Sensory neuropathy was the primary toxicity (45.4% qw, 38.1% q3w; p = 0.62). Clinical benefit was observed in most women (76.2% qw, 57.1% q3w; p = 0.20). Women receiving nab-paclitaxel had a median overall survival of 13.6 months qw (range: 8.1-28.3 months) and 10.8 months q3w (range: 5.9-17.9 months; p = 0.03). Regardless of dosing schedule, women experiencing clinical benefit lived significantly longer than those not experiencing a benefit (17.3 months vs. 7.7 months; hazard ratio: 0.14; 95% confidence interval: 0.06 to 0.33). CONCLUSIONS: Our clinical experience demonstrates that most women treated with nab-paclitaxel experienced some clinical benefit. Patients achieving clinical benefit lived significantly longer than those who did not. Nab-paclitaxel was well tolerated, with the primary toxicity being mild sensory neuropathy. Nab-paclitaxel represents another treatment option, with a favourable toxicity profile, for women with mbc.

Clinical trial design in biosimilar drug development.

In contrast to most drugs which are chemically synthesized and have a known structure, biological drugs are derived from living organisms or their products. Biologicals are structurally more complex and unique from chemically synthesized small drug molecules because of their larger size and intricate manufacturing process. Secondary to their protein structure, they are also more prone to acute and chronic immune responses. Biosimilars are intended to offer comparable safety and efficacy relative to reference brand biologicals, yet they are not generic alternatives to the original compounds and so are currently not considered interchangeable. Given their structural complexity, multifaceted manufacturing processes and risk for immunogenicity, biosimilars require class-specific regulatory approval pathways. Here we seek to provide a general overview of clinical trial design in the era of biosimilar drug development. This will include a review of the regulatory requirements for clinical trials in Europe and the United States, followed by a review of two biosimilars that have recently reported results of randomized trials against branded biologicals.

Use and delivery of granulocyte colony-stimulating factor in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy-single-centre experience.

BACKGROUND: Use of granulocyte colony-stimulating factor (g-csf) as primary prophylaxis against chemotherapy-induced neutropenia has significant cost implications. We examined use of g-csf for early-stage breast cancer patients at our centre. The study also examined the pattern of nurse-led patient teaching with respect to drug self-administration. METHODS: Patients who received g-csf between November 2009 and October 2010 were identified from pharmacy records. After consent had been obtained, electronic charts were examined to extract data on chemotherapy and use of g-csf. Patients were contacted by telephone to obtain information on the utilization of home-care nursing visits for g-csf administration. RESULTS: The study analyzed 36 patients. Median age was 58 years (range: 31-78 years). Of the 36 patients, 30 (83%) had received adjuvant treatment, and 6 (17%), neoadjuvant treatment. Most patients (71%) received 10 days (range: 7-10 days) of filgrastim. Of the 36 patients, 29 (81%) received g-csf as primary prophylaxis. In 90% of those patients, primary prophylaxis commenced with the taxane component of treatment. Of the 36 patients, 7 (19%) received g-csf after neutropenia, including 2 who had febrile neutropenia. In 96% of the patients, injections were received at home with the help of a nurse; those patients were subsequently taught self-injection techniques. The median number of nursing visits was 2 (range: 1-3 visits). Most patients were satisfied with the home care and g-csf teaching they received. CONCLUSIONS: Most of the g-csf used in breast cancer treatment during the study period was given for primary prophylaxis. A major reason for the decision to use g-csf appears to have been physician-perceived risk of febrile neutropenia. Delivery of g-csf by home-care nurses was well received by patients.

Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib.

BACKGROUND: This study describes a repeated measures prediction index to identify patients at high risk of ≥grade 2 hand-foot skin reaction (HFSR) before each week of sorafenib therapy. METHODS: Data from 451 patients who received a sorafenib (400 mg bid) as part of a clinical trial were reviewed (Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125-134). Generalized estimating equations were used to develop the final risk model. A risk-scoring algorithm (range 0-58) was then derived from the final model coefficients. External validation was then carried out on a new sample of 1145 patients who received sorafenib under an expanded access program. RESULTS: Pretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and number of affected organs were predictors for ≥grade 2 HFSR. A nonlinear association between HFSR risk and treatment duration was also identified where risk was maximized at week 5 followed by a gradual decline. Before each week of therapy, patients with risk scores>40 would be considered at high risk for developing ≥grade 2 HFSR. CONCLUSIONS: The application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.

Prospective validation of risk prediction indexes for acute and delayed chemotherapy-induced nausea and vomiting.

BACKGROUND: Despite the use of standardized anti-emetic guidelines, up to 20% of cancer patients suffer from moderate-to-severe chemotherapy-induced nausea and vomiting (cinv)-that is, grade 2 or greater according to the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. We previously developed cycle-based prediction models and associated scoring systems for acute and delayed cinv. As part of the validation process, we prospectively evaluated the ability of the scoring systems to accurately identify patients deemed to be high risk for grade 2 or greater cinv. METHODS: Patients who were receiving any chemotherapy for solid tumours and who consented to participate were provided with symptom diaries. Compliance to the diaries was enhanced by 24-hour and 5-day telephone callbacks after chemotherapy in every cycle. All patients received anti-emetic prophylaxis as prescribed by the treating physician. Before each cycle of chemotherapy, the acute and delayed cinv scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression modelling was then applied to compare the risk for grade 2 or greater cinv between patients considered to be at high and at low risk. The external validity of each system was also assessed using an area under the receiver operating characteristic curve (auroc) analysis. RESULTS: We collected cinv outcomes data from 95 patients during 181 cycles of chemotherapy. The incidence of grade 2 or greater acute and delayed cinv was 17.7% and 18.2% respectively. As previously identified, major predictors for grade 2 or greater cinv included younger patient age, platinum- or anthracycline-based chemotherapy, low alcohol consumption, earlier cycles of chemotherapy, previous history of morning sickness, and prior emetic episodes after chemotherapy. The acute and delayed scoring systems both had good predictive accuracy when applied to the external validation sample (acute-auroc: 0.69; 95% confidence interval: 0.59 to 0.79; delayed-auroc: 0.70; 95% confidence interval: 0.60 to 0.80). Patients identified by the scoring systems to be at high risk were 2.8 (p = 0.025) and 3.1 (p = 0.001) times more likely to develop grade 2 or greater acute and delayed cinv. CONCLUSIONS: The present study demonstrates that our scoring systems are able to accurately identify patients at high risk for acute and delayed cinv. Application and planned continued refinement of the scoring systems will be an important means of patient-specific risk assessment that will allow for optimization of anti-emetic therapy.

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador.

BACKGROUND: In 2005, bevacizumab was approved by Health Canada for patients with metastatic colorectal cancer (mCRC). Newfoundland and Labrador was one of the first Canadian provinces to fund this agent in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) chemotherapy. In this analysis, the entire provincial bevacizumab sample for the first 2 years was assessed for overall safety and efficacy. METHODS: The medical records of 43 patients with mCRC who had received FOLFIRI with bevacizumab were identified and reviewed. The longitudinal data collection format that was adopted assessed occurrences of adverse events after each cycle of treatment. Toxicity outcomes such as gastrointestinal (GI) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (VTEs) were collected and graded using the U.S. National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Time to treatment failure (TTF) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Overall, the 43 study patients received 398 cycles of anticancer therapy (median: 6 cycles; range: 1-24 cycles). No gi perforations were identified. However, 4 bleeding events occurred (9.3%), 3 requiring permanent discontinuation of bevacizumab. Also, 6 grade 3 or 4 VTEs occurred (14.0%), 3 of which required a hospital admission. In addition, grades 3 and 4 diarrhea, febrile neutropenia, and proteinuria showed cumulative incidences of 11.6%, 2.3%, and 2.3% respectively. Median TTF was 6.3 months; median os was 24.4 months. CONCLUSIONS: Bevacizumab in combination with FOLFIRI appears to be well tolerated, and efficacy is consistent with trial reports. However, patients should be closely monitored to avoid potentially serious events such as bleeding and VTEs.

Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: a retrospective, outcomes-based survey.

INTRODUCTION: With the widespread use of sequential anthracycline/taxane-based chemotherapy for early-stage breast cancer, clinicians are becoming rapidly aware of toxicities associated with those regimens. Despite the low incidence reported in the literature of significant arthralgia and myalgia with those regimens, it is clinically evident that a substantial proportion of patients develop such toxicities. We performed a pilot study to investigate the extent of this problem. PATIENTS AND METHODS: Patients who had received prior adjuvant or neoadjuvant chemotherapy [doxorubicin-cyclophosphamide followed by paclitaxel (AC-T), doxorubicin-cyclophosphamide followed by docetaxel (AC-D), or 5-fluourouracil-epirubicin-cyclophosphamide followed by docetaxel (FEC-D)] completed a retrospective outcomes-based survey. The survey utilized the Functional Assessment of Cancer Therapy-Taxane Scale, the Memorial Symptom Assessment Scale, and a modified Brief Pain Inventory. RESULTS: Interviews were conducted with 82 patients. Interviewees had received AC-T (43%), FEC-D (43%), and AC-D (14%). Pain as a side effect of either the anthracycline or the taxane chemotherapy was reported by 87% of patients. Most of the patients (79%) indicated that their worst pain occurred during the taxane component of treatment. Compared with paclitaxel, docetaxel was reported to cause more pain. Narcotics for pain management were required by 35 of 82 patients (43%). CONCLUSIONS: A significant number of patients receiving sequential anthracycline/taxane-based chemotherapy for early-stage breast cancer experience pain, particularly during the taxane component. Prospective patient-reported outcome assessments are needed to help individualize treatment interventions and to improve symptom management in this population.