Background Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin’s influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study. Methods 2,066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n=84); women with diabetes with no metformin use (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40 –1.38, p=0.67) and to women without diabetes (HR 1.00; 95% CI 0.61 – 1.66, p=0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38 – 1.55, p=0.47) and for overall survival was 0.86 (95% CI 0.49 – 1.52; p=0.60). Conclusions In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.

Background Metformin has been associated with improved CRC survival, but investigations are limited by small numbers of patients and confounding by diabetic severity. We examined the association between metformin use and overall survival (OS) in patients with diabetes and CRC in a large population of U.S. veterans, while adjusting for measures of diabetic severity. Methods Patients diagnosed with CRC from 1/2001-12/2008 were identified from the Veterans Affairs Central Cancer Registry. Multivariable models were used to examine the adjusted association of OS with diabetes and use of anti-diabetic medications. Results 21352 patients diagnosed with CRC were identified (n=16355 non-diabetic patients, n=2038 diabetic patients on metformin, n=2136 diabetic patients on medications other than metformin, n=823 diabetic patients not on anti-diabetic medication). Diabetic patients had a significantly worse OS than non-diabetic patients, but metformin users had only a 10% increase in death (HRadj 1.10; 95% CI 1.03-1.17, p=0.004), as compared to 22% for users of other anti-diabetic medications (HRadj 1.22; 95% CI 1.15-1.29, p<0.0001). Among CRC patients with diabetes, metformin users had a 13% improved OS versus patients taking other anti-diabetic medications (HRadj 0.87; 95% CI 0.79-0.95, p=0.003), while diabetic patients not on any anti-diabetic medications did not differ with respect to OS (HRadj 1.02; 95% CI 0.90-1.15, p=0.76). Conclusion Among diabetics with CRC, metformin use is associated with improved survival, despite adjustments for diabetes severity and other risk factors. Impact These data lend further support to the conduct of randomized studies of possible anti-cancer effects of metformin among patients with CRC.

Systemic immunoglobulin light chain (AL) amyloidosis is a rare but fatal disease. It results from clonal proliferation of plasma cells with excessive production of insoluble misfolded proteins that aggregate in the extracellular matrix, causing damage to the normal architecture and function of various organs. For decades, treatment for AL amyloidosis was based mainly on therapeutic agents previously studied for its more common counterpart, multiple myeloma. As the prevalence and incidence of AL amyloidosis have increased, ongoing research has been conducted with treatments typically used in myeloma with varying success. In this review, we focus on current treatment strategies and updates to clinical guidelines and therapeutics for AL amyloidosis.

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Hypoxic lung injury during cancer therapy poses a serious problem. Multiple agents can be implicated. In this patient, vinorelbine most likely was the causative agent of the pulmonary findings. While filgrastim has been associated with hypoxemia during neutrophil recovery, 1,2 the lack of temporal association, leukocytosis, or positive rechallenge during subsequent chemotherapy makes it an unlikely offender in this case. No other causes could be elucidated after extensive work-up, though remote history of radiotherapy to the chest wall may have been a sensitizing factor. In a pooled analysis of three large multicenter trials conducted in North America with vinorelbine (n ϭ 327), dyspnea was reported in 5% of patients; in 3% it was severe. 3 This complication may occur after either the first or subsequent treatments. In fact, it may manifest as late as on the tenth cycle of treatment. 4,5 Potential risk factors include concomitant use of mitomycin-C and history of dyspnea from a previous infusion. 5,6 Two types of respiratory distress associated with vinorelbine have been reported: acute and subacute. The acute form, typically associated with acute dyspnea, bronchospasm, fever, hypotension, and alveolar infiltrates, usually occurs within minutes after vinorelbine infusion. 3,6 The subacute form, occurring hours to days after infusion, is marked by progressive dyspnea, diffuse interstitial infiltrates, and in rare cases, acute respiratory distress syndrome. 7 Vinorelbine, a semisynthetic vinca alkaloid, interacts with tubulin. It causes imbalance between polymerization and depolymerization and leads to a disruption of microtubule assembly-an essential component of vascular permeability regulation. 8 Microtubule inhibitors cause a dysfunctional actomyosin cytoskeleton, leading to endothelial cell barrier dysfunction, which is similar to the pathogenesis of many conditions such as sepsis and acute lung injury. 8 After infusion, vinorelbine achieves much higher concentration in heart and lung tissues than in serum. 9 In fact, rare cases of myocardial infarction have also been reported in association with vinorelbine. 10,11 Treatment of acute lung injury associated with vinorelbine or other suspected chemotherapeu-tic agents is largely supportive, and most reports recommend the use of corticosteroids. Typically, respiratory distress associated with single-agent vinorelbine is followed by full recovery. This syndrome, as with other vinca alkaloids such as vinblastine, may result in chronic lung disease, especially when mitomycin-C was concurrently administered. 12 After one episode of respiratory distress, re-treatment with vinorelbine may lead to a more severe reaction, though some investigators re-treated patients, noting only a mild reaction, using premedication with corticosteroids. 3,6 Vinorelbine most likely was the causative agent in this patient, and while resulting in a critical situation, was associated with a full recovery. As the role for vinorelbine in solid tumors, including breast cancer, continue...