Capecitabine as Maintenance Therapy for High-Risk, Resected Colorectal Cancer.

INTRODUCTION: In 2020, colorectal cancer will be the fourth most frequently diagnosed malignant neoplasm and the second leading cause of site-specific, cancer-related deaths in the USA. Notably, 80% of the new cases are, by staging criteria, potentially curable even those with completely resected stage 4 disease. If slightly more than half the losses can be attributed to metastatic disease at presentation, then the remaining portion of deaths may be linked to disease relapse after surgery and, if applicable, adjuvant chemotherapy. The inference that these therapies are not curative for a significant number of subjects poses a role for maintenance therapy. OBJECTIVE: To assess event-free survival (EFS) of patients who received capecitabine as maintenance therapy following treatment according to current guidelines. METHODS: Clinical outcomes data were collected for 35 subjects treated with capecitabine as maintenance therapy. Descriptive statistical analyses were conducted on collective data related to duration of maintenance therapy and disease or clinical status from surgery to initial event. Kaplan-Meier method and log-rank test were used to analyze EFS and overall survival. RESULTS: Of the entire cohort, 26 subjects have no evidence of disease (NED), a median of 5.5 years from surgery. Kaplan-Meier analyses indicated a 5-year EFS rate of 74% (95% CI: 60-90%). Eighteen of these 26 patients received capecitabine ≥30 months. Eight of the 17 subjects treated with capecitabine therapy for <30 months developed progressive disease; the majority of the relapses occurred within 20 months of surgery. The difference between the two groups was statistically significant. Six subjects died, only two of who had metastatic disease at the time of death; the other four had NED at least 4 years from surgery. Five patients with resected stage 4 disease who received capecitabine as maintenance therapy were alive >5 years from surgery. CONCLUSION: The findings and analyses of this cohort of patients suggest that maintenance capecitabine therapy reduces the risk of disease progression and cancer-related death.

Efficacy of solubilized vemurafenib administered via nasogastric tube.

Until only a few years ago, there was only one truly effective therapy for patients with metastatic melanoma. While long-term remission could be achieved in some patients, toxicities associated with high-dose IL-2 were significant. New insight related to molecular pathways of tumor cells indicated that an activating mutation of BRAF can be found in approximately 50-60% of all patients with melanoma. Proof-of-concept demonstrated in clinical trials of a drug targeting mutant BRAF led to the approval of vemurafenib by the US FDA in August 2011. Supplied in an oral dosage form, we provide an alternative method of administering vemurafenib in a patient unable to take anything by mouth.

A phase 2 trial of ixabepilone plus cetuximab in first-line treatment of metastatic pancreatic cancer.

BACKGROUND: The aim of this phase 2 study was to evaluate the safety and efficacy of ixabepilone plus cetuximab in patients with advanced pancreatic cancer. METHODS: Eligible patients had advanced pancreatic adenocarcinoma that was metastatic or not amenable to resection, a Karnofsky performance status ≥70%, and no prior therapy for advanced disease. Patients received ixabepilone 32 mg/m(2) (3-hour IV infusion) every 3 weeks and cetuximab 250 mg/m(2) (1-hour IV infusion) weekly. The primary efficacy end point was the 6-month survival rate. Secondary end points included tumor response rate, overall survival, progression-free survival, and tolerability. RESULTS: A total of 54 patients were enrolled on this study. The 6-month survival rate was 57% (31/54: 95% CI: 43-71%) with a median overall survival of 7.6 months (95% CI: 5.5-12.2 months). Patients who developed acneiform rash (n = 36) had a median survival of 8.8 months, compared with 2.6 months for those without rash (n = 18). Of 31 patients with measurable disease (defined as response-evaluable), 4 had confirmed partial responses and an additional 24 had stable disease. The combination was generally well-tolerated with the most common grade 3/4 hematological toxicities being leucopenia (39%) and neutropenia (33%). The most common grade 3/4 nonhematologic toxicity was fatigue (17%). CONCLUSIONS: The combination of ixabepilone and cetuximab was active and had acceptable toxicity. The efficacy results are similar to single-agent ixabepilone and gemcitabine-based combination therapies in patients with advanced pancreatic cancer. Exploratory analyses suggest a trend toward improved survival for patients who experienced rash.

Identification of a novel marker associated with risk for delayed chemotherapy-induced vomiting.

PURPOSE: Besides chemotherapy drugs, a number of patient-related factors (i.e., gender, age, history of alcohol consumption, and/or motion sickness) may be used to calculate the risk for chemotherapy-induced vomiting. We evaluated data with the intent of identifying a unique variable associated with delayed vomiting in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: From an ongoing research study, the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA), creatinine, and substance P were measured over a 72-h period in 25 patients receiving MEC. All patients were treated with a 5-hydroxytryptamine-3 receptor antagonist plus dexamethasone according to published guidelines; none received aprepitant prophylactically. Urine 5-HIAA/creatinine and serum substance P values were grouped according to the development (+) or absence (-) of delayed emesis. Baseline mean values associated with the two neurotransmitters were analyzed by analysis of variance. RESULTS: Eleven patients developed moderate to severe delayed vomiting; the other 14 were symptom-free. The pretreatment log (mean 5-HIAA/creatinine) was 1.22 and 1.81 in the (+) and (-) emesis groups, respectively, p = 0.0049; the pretreatment log (mean substance P) for the same respective groups was 5.33 and 4.09 pg/mL, p > 0.05. The log (mean ratio of substance P to 5-HIAA/creatinine) between-group difference in those with and without emesis was 4.53 and 2.52, respectively, p = 0.0002. The 5-HIAA/creatinine and ratio of substance P to 5-HIAA/creatinine data were also used to determine cutoff points which resulted in the optimal predictive accuracy. CONCLUSIONS: These preliminary findings suggest that an elevated pretreatment ratio of substance P to 5-HIAA/creatinine >70 is associated with the development of delayed vomiting induced by MEC.

Concordance between substance P levels and antiemetic guidelines.

Practice guidelines now include an antagonist of the substance P/NK1 (neurokinin 1) receptor pathway as part of the standard antiemetic regimen for patients receiving highly, as well as certain moderately, emetogenic chemotherapy regimens. Accumulated laboratory data were used to determine the degree of concordance between substance P levels and the current antiemetic guidelines. Five blood samples were collected over 72 hours from 22 adult patients treated with cisplatin-containing chemotherapy regimens. Overall, the mean baseline substance P level was 318 pg/mL. Although increases in substance P were observed during both phases of the emetic response, analysis by least squares means grouped by cisplatin dosage and vomiting phase was significantly different (P< 0.0001). Preliminary analysis of substance P levels appears to provide additional justification for including the NK1 receptor antagonist in the current antiemetic practice guidelines. In addition, these data provide biochemical justification for the cisplatin dosage criterion used in clinical trials.

Priorities and uncertainties of administering chemotherapy in a pregnant woman with newly diagnosed colorectal cancer.

BACKGROUND: The absence of treatment standards for the use of chemotherapy in pregnancy is due, in part, to the fact that cancer in the gravid female is relatively uncommon. METHOD: A case (of a pregnant woman with newly diagnosed colorectal cancer) is presented to explore this area of medical uncertainty. RESULT: Managed by a multi-disciplinary team, successful prolongation of gestation was achieved with an oxaliplatin-based chemotherapy regimen. CONCLUSION: A perspective of the ongoing conflict between prolonging the mother's life and preserving fetal development is highlighted. Although not life-saving, administration of chemotherapy in this woman was life-sparing.

5-Hydroxyindoleacetic acid and substance P profiles in patients receiving emetogenic chemotherapy.

BACKGROUND: Even though direct cause and effect has not been proved, clinical evidence suggests serotonin and substance P (SP) are involved in the emetic response following chemotherapy. Because of several parallels, we hypothesized that SP release, like serotonin, may be propagated by chemotherapy and both substances can be measured in biological fluids, and correlated with a particular phase of emesis. METHODS: Urinary 5-hydroxyindoleacetic acid (5-HIAA) was assessed by HPLC; serum and urine SP were measured by immunoassay. In addition to construction of neurotransmitter profiles, all SP data were grouped according to cisplatin dosages, = or >75 mg/m(2) versus <75 mg/m(2), and phase of emesis, acute versus delayed. Analyses of these data were performed by repeated measures analysis of variance. RESULTS: Samples were collected over a 72-hour period from 26 adult patients who received cisplatin- (n = 13) or non-cisplatin-containing (n = 13) chemotherapy. Mean baseline 5-HIAA: creatinine ratios were 5.23 and 5.16 in females and males, respectively; mean baseline SP levels were 392 and 181 pg/mL in females and males, respectively. Comparisons between SP data stratified by cisplatin dosage and emetic phase were significantly different, P < 0.0001. CONCLUSIONS: Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.

Partial 7q Isochromosome in Bone Marrow Following Treatment of Hodgkin's Disease.

We report on a 29-year-old female followed for relapsed Hodgkin's disease. She had been diagnosed with Hodgkin's disease at 20 years of age and had been treated with chemotherapy. She had been in remission for six years when she relapsed, at which time she received chemotherapy for bone marrow transplant (BMT). After failure of BMT, she received additional chemotherapies with growth factors and radiation treatment. A bone marrow biopsy showed moderate hypercellularity with erythroid hyperplasia, but the karyotype had an abnormal clone containing an isochromosome derived from a 7q22 deletion.