Peter T. Silberstein

Intravenous Calcium and Magnesium for Oxaliplatin-Induced Sensory Neurotoxicity in Adjuvant Colon Cancer: NCCTG N04C7

PURPOSE Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT. METHODS Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect. RESULTS Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo. CONCLUSION Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.

Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial

PURPOSE Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. PATIENTS AND METHODS Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. RESULTS In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. CONCLUSION This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous Iron in patients with chemotherapy-induced anemia†

This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double‐blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL−1, and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL−1). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT‐F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan–Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients. Am. J. Hematol., 2010.

Effect of palliative care services on the aggressiveness of end-of-life care in the Veteran's Affairs cancer population.

BACKGROUND Cancer care near the end of life (EOL) has become more aggressive over the years. Palliative care services (PCS) may decrease this aggressive cancer care in terminally ill cancer patients. Our objective was to observe the aggressiveness of cancer care near the EOL among Veterans Affairs cancer patients before and after the institution of a PCS team. We also assessed the time taken prior to death to initiate a PCS consultation and its effect on the aggressiveness of cancer care near the EOL. METHODS This is a retrospective chart review analysis performed at the local Veterans Affairs hospital looking at the last 100 patients in each of the years, 2002 and 2008, who died with active cancer. Only patients in 2008 had access to a PCS team. RESULTS In the last 30 days of life, compared to 2002, patients in 2008 had a higher incidence of: chemotherapy administration, more than one hospital admission, more than 14 days of hospital stay, intensive care unit admissions, and in-hospital deaths. Patients with timely PCS consults in 2008 appeared to have a lower incidence of: chemotherapy administration, more than one emergency department visit, more than one hospital admission, more than 14-day hospital stays, intensive care unit admissions, and deaths in the hospital. Timely PCS consults were associated with earlier and more frequent hospice referral. CONCLUSIONS Cancer care near the EOL has become more aggressive with time at one of the hospitals in the Veterans Affairs healthcare system (VAHS). Institution of a PCS service was unable to completely decrease this trend of increasing aggressiveness of cancer care near the EOL. However, timely PCS consults may help attenuate this aggressiveness.

Clinicopathologic factors associated with lymph node retrieval in resectable colon cancer: A veterans' affairs central cancer registry (VACCR) database analysis

A long‐term determinant of survival in resectable colon cancer is the involvement of regional lymph nodes. We evaluated the clinicopathologic factors associated with lymph node retrieval.

Association between race and survival of patients with non--small-cell lung cancer in the United States veterans affairs population.

BACKGROUND Racial disparities in outcomes of non-small-cell lung cancer (NSCLC) patients in the United States are well documented. A retrospective analysis of patients in the Veterans Affairs Central Cancer Registry was conducted to determine whether similar disparities exist in a population with a single-payer, accessible health care system. PATIENTS AND METHODS Demographic data of patients diagnosed with NSCLC between January 1995 and February 2009 were analyzed using Kruskal-Wallis test or the χ(2) test. Multivariate Cox proportional hazards regression analysis was used to compare survival among races. RESULTS Of the 82,414 patients, 98% were male, 82% had a smoking history, and 81% were Caucasian. Caucasian individuals had better prognostic features compared with African-American individuals (stage I/II [24% vs. 21%]; Grade I/II [21% vs. 17%]). A larger proportion of Caucasian compared with African-American individuals received stage-appropriate treatment (surgery for stage I [48% vs. 41%; P < .001]; chemotherapy for stage IV [18% vs. 16%; P = .003]). African-American individuals had a lower risk of mortality compared with Caucasian individuals (hazard ratio, 0.94; 95% confidence interval, 0.92-0.96). CONCLUSION Although African-American patients had a higher stage and grade of NSCLC, they had a better overall survival than Caucasian patients. In a single-payer system with accessible health care, previously described racial differences in lung cancer outcomes were not observed.

Assessment of prognostic factors after primary tumor resection in metastatic colon cancer patients: A Veteran's Affairs Central Cancer Registry (VACCR) analysis, 1995–2008

Resection of the primary tumor in metastatic colon cancer may occur for palliation of bleeding or obstruction despite distant metastases. This study evaluates clinicopathologic features that serve as prognostic markers in those patients with stage IV colon cancer who undergo resection of their primary tumor.

Proton pump induced thrombocytopenia: A case report and review of literature.

Abstract Proton pump inhibitors (PPIs) are not widely recognized as a cause of drug-induced thrombocytopenia. Literature is mainly confined to case reports and has been insufficient to explore the possibility that this adverse event may be attributed to a class effect of PPI therapy. We present a case where platelet counts dropped from 177 (×103 per mm3) to 47 (×103 per mm3) within 6 days after the patient was switched from omeprazole to pantoprazole. There have been case reports of thrombocytopenia caused by PPIs; however, this is noted to be extremely rare. In our case, the patient developed thrombocytopenia on two separate occasions of exposure to pantoprazole, which resolved after stopping the medicine, thus providing definite proof of pantoprazole causing thrombocytopenia. Moreover, the patient did not have thrombocytopenia with omeprazole, thus suggesting that thrombocytopenia with PPIs might be an individual drug effect rather than a class effect. This occurrence has been reported in three other case reports as well. From the nine case reports that we have reviewed, direct causal relationship was found in a few reports only. It has been hypothesized that this adverse effect may be immune mediated, but further investigations are still needed to identify the exact pathogenesis.

Neoadjuvant treatment of Dermatofibrosarcoma Protuberans of pancreas with Imatinib: case report and systematic review of literature

Dermatofibrosarcoma Protuberans (DFSP) is a rare skin tumor, characterized by frequent local recurrence but is seldom metastatic. It is histologically characterized by storiform arrangement of spindle cells. Cytogenetically, most tumors are characterized by translocation 17:22 leading to overexpression of tyrosine kinase PDGFB which can be targeted with tyrosine kinase inhibitor, Imatinib. We describe the first case of unresectable pancreatic metastases from DFSP treated with neoadjuvant Imatinib and subsequently R0 metastectomy. Additionally, a comprehensive systematic review of DFSP pancreatic metastases and the current published data on the use of Imatinib in DFSP is summarized.

Heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially serious complication of …