The effects of extended photoperiod and warmth on hair growth in ponies and horses at different times of year.

Photoperiod is considered the most dominant environmental cue allowing animals to anticipate and adapt to seasonal changes. In seasonally breeding mammals, changes in daylength alter pineal melatonin secretion and pituitary prolactin secretion. During the seasonal transition to shorter winter daylengths, increased production of melatonin and declining prolactin are associated with triggering winter coat growth in many animals. Similarly, studies have shown that artificial extension of photoperiod suppresses melatonin secretion and lifts prolactin inhibition to activate moulting. Four longitudinal cohort studies were conducted to determine if extended photoperiod and warmth, provided by mobile light masks and rugs (horse blankets), could reverse the onset of winter coat growth, maintain the summer coat and accelerate winter coat shedding in horses and in ponies. Studies began at dates corresponding to the autumnal equinox, one month post-summer solstice, one month pre-winter solstice and one month post-winter solstice, respectively. To extend photoperiod to approximately 15h of light, commercially available head-worn light masks provided low intensity blue light to one eye until 11pm daily. Coat condition and shedding rate were scored and hair samples collected, measured and weighed bi-weekly. Data from control and treatment groups were analysed by repeated measures ANOVA. Results revealed that extended photoperiod 1) did not reverse winter coat growth when initiated at the autumnal equinox, 2) effectively maintained the summer coat in stabled horses when initiated one month post-summer solstice, 3) accelerated shedding in outdoor living horses when initiated one month pre-winter solstice and 4) did not accelerate shedding in indoor or outdoor living ponies when initiated one month post-winter solstice. To successfully manage equine coat growth while also preserving optimal thermoregulation in both competition and breeding stock correct timing of light application is crucial and requires careful monitoring of environmental temperature. Further studies are needed where variations in breed and management are considered.

CE: Late and Long-Term Sequelae of Breast Cancer Treatment.

: More than 12% of women will be diagnosed with breast cancer at some point in their lives, and 78% of them can be expected to survive for at least 15 years. More than 2.8 million breast cancer survivors currently reside in the United States. After breast cancer treatment, as many as 90% of survivors report physical problems that can reduce functional ability, produce or exacerbate emotional problems, negatively affect body image, and diminish quality of life. Many survivors will seek care for late and long-term effects of treatment, which will not necessarily be recognized as such by health care providers and appropriately treated. In this article, the authors discuss the underlying causes of late and long-term sequelae of breast cancer treatment and describe effective assessment and management strategies. They focus specifically on the most common and potentially debilitating upper body effects of breast cancer surgery and external radiation therapy: lymphedema, axillary web syndrome, postmastectomy pain syndrome, rotator cuff syndrome, adhesive capsulitis, arthralgias, cervical radiculopathy, and brachial plexopathy.

The Role of Advanced Practice Nurses in Cancer Survivorship Care.

OBJECTIVES: To review advanced practice nursing roles in planning, implementing, and evaluating survivorship care. DATA SOURCES: Review of the literature, published articles, government and organizational reports. CONCLUSION: The increased focus on improving post-treatment cancer care presents opportunities for advanced practice nurses to meet the physical and psychosocial needs of cancer survivors. IMPLICATIONS FOR NURSING PRACTICE: As experts in the comprehensive delivery of care, oncology advanced practice nurses are positioned to initiate, deliver, and evaluate survivorship care through innovative models.

Pralatrexate with vitamin supplementation in patients with previously treated, advanced non-small cell lung cancer: safety and efficacy in a phase 1 trial.

INTRODUCTION: Pralatrexate is an antifolate designed for preferential tumor cell uptake and accumulation and received accelerated Food and Drug Administration approval in relapsed/refractory peripheral T-cell lymphoma. Pralatrexate 135 to 150 mg/m(2) every 2 weeks without vitamin supplementation was active in non-small cell lung cancer (NSCLC) although mucositis was dose limiting. This phase 1 study evaluated the safety of higher pralatrexate doses with vitamin supplementation to minimize toxicities. METHODS: Patients with stage IIIB/IV NSCLC received pralatrexate 150 to 325 mg/m(2) every 2 weeks with folic acid and vitamin B12 supplementation. Outcomes measured included adverse events (AEs), pharmacokinetics, and radiologic response. RESULTS: Thirty-nine patients were treated for a median of two cycles (range 1-16+). Common treatment-related grade 3 and 4 AEs by dose (≤190 mg/m(2) and >190 mg/m(2)) included mucositis (33 and 40%) and fatigue (11 and 17%). Treatment-related serious AE (SAE) rates for doses ≤190 and >190 mg/m(2) were 0 and 20%, respectively. The response rate was 10% (95% confidence interval: 1-20%), including two patients with complete response (26+ and 32+ months) and two with partial response. Serum pralatrexate concentrations increased dose dependently up to 230 mg/m(2). CONCLUSIONS: Pralatrexate with vitamin supplementation was safely administered to patients with previously treated NSCLC, and durable responses were observed. The recommended starting dose for phase 2 is 190 mg/m(2). A similar safety profile was observed in patients treated at 230 mg/m(2), although a higher serious AE rate was evident. Mucositis remains the dose-limiting toxicity of pralatrexate, and this study failed to demonstrate that vitamin supplementation prevents mucositis and failed to identify clinical predictors of mucositis. Individualized dose-modification strategies and prospective mucositis management will be necessary in future trials.

A phase II tolerability study of cisplatin plus docetaxel as adjuvant chemotherapy for resected non-small cell lung cancer.

INTRODUCTION: We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer. METHODS: The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data. The first cohort was treated with docetaxel 35 mg/m2 intravenously (IV) on days 1, 8, and 15, and cisplatin 80 mg/m2 IV on day 15, every 4 weeks for four planned cycles. A second cohort was treated with docetaxel 75 mg/m2 IV plus cisplatin 80 mg/m2 IV on day 1 every 3 weeks for four planned cycles. RESULTS: Sixteen patients were treated with weekly docetaxel and cisplatin every 4 weeks, with five of 16 (31%) unable to complete three cycles. Subsequently, 11 patients were treated with docetaxel and cisplatin every 3 weeks, with six of 11 (55%) unable to complete three cycles. Among the 11 patients who failed to complete three cycles, the reasons for stopping included one or more of the following: fatigue (n = 8), nausea (n = 4), febrile neutropenia (n = 1), hypotension (n = 1), and nephrotoxicity (n = 1). CONCLUSIONS: The combination of cisplatin at 80 mg/m2 with docetaxel 35 mg/m2 weekly or 75 mg/m2 every 3 weeks is no better tolerated than older chemotherapy regimens. The most common reason to stop chemotherapy was intolerable fatigue. These results suggest that the most common dose-limiting toxicities are attributable to the cisplatin, given similar problems were encountered whether the docetaxel was delivered as a single dose every 3 weeks or as a lower weekly dose.

A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors.

PURPOSE: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer. EXPERIMENTAL DESIGN: Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B(12) and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation. RESULTS: For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m(2) plus docetaxel 35 mg/m(2) administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non-small-cell lung cancer. CONCLUSIONS: Pralatrexate (120 mg/m(2)) plus docetaxel (35 mg/m(2)) plus vitamin supplementation is well tolerated with signs of efficacy against non-small-cell lung cancer that merit phase 2 testing.

A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer.

BACKGROUND: Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial. RESULTS: Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2-22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS: Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study.

Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial.

BACKGROUND: Imatinib inhibits the c-kit tyrosine kinase, which, accounts for its activity in gastrointestinal stromal tumors. The presence of c-kit protein expression in small cell lung carcinoma (SCLC) tumor specimens, as well as in vitro data supporting the role of c-kit in autocrine and paracrine growth stimulation specifically in SCLC, provided a rationale for studying imatinib in this disease. The authors conducted a Phase II single-institution study of imatinib in patients with recurrent SCLC whose tumor specimens expressed c-kit protein. METHODS: Patients with progressive SCLC after one or two previous chemotherapy regimens consented to have their tumor specimens screened by immunoperoxidase stain (CD117, Dako Corporation, Carpinteria, CA) for c-kit protein expression. If present, individuals were then eligible for treatment with an imatinib dose of 400 mg orally twice daily (total, 800 mg per day). RESULTS: The presence of c-kit protein was assessable in 36 of 39 (92%) tumor samples. Twenty-eight (78%) tumor samples had immunohistochemical staining for c-kit protein. Twelve patients were enrolled in the treatment portion of the current study. No responses were observed, and all patients had disease progression by Week 4. Edema, fatigue, nausea, and electrolyte abnormalities were the primary toxicities. CONCLUSIONS: Imatinib did not have antitumor activity against SCLC, even with c-kit protein present in tumor specimens. The dismal prognosis for these patients with progressive SCLC emphasized the urgent need for continued studies of new therapies in this population.