Appropriate vitamin D loading regimen for patients with advanced lung cancer.

BACKGROUND: Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens. METHODS: In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy. RESULTS: Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol. CONCLUSION: Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

Should patient-rated performance status affect treatment decisions in advanced lung cancer?

INTRODUCTION: The Eastern Cooperative Oncology Group (ECOG) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials. The patient-rated performance status score (Pt-PS), section of the patient generated subjective global assessment scale, has identical criteria to the physician-rated ECOG scale (MD-PS). We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial. METHODS: Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated questionnaire, which was then correlated (kappa statistic) with the ECOG PS recorded at the same time. Patients were treated with standard chemotherapy. Survival was determined using Kaplan-Meier statistics. RESULTS: One hundred nine patients (M:F-54:55) were recruited. Pt-PS differed from MD-PS in 59 (54%) instances (p = 0.0001). When scores were not congruent, 41/59 (69%) patients evaluated themselves as having a worse PS than the physician's rating. Pt-PS was 0 to 1 in 60 (55%) patients whereas MD-PS was 0 to 1 in 78 (72%) patients. The functional status irrespective of evaluator was predictive of survival (p = 0.001 for MD-PS and p = 0.001 for Pt-PS). However, the median survival in those with MD-PS >/=2 was 3.3 (CI; 1.7-4.9) months whereas individuals with Pt-PS >/=2 had a median survival of 6.2 (CI; 5.4-6.9) months. CONCLUSIONS: Pt-PS and MD-PS were not congruent in over half of the cases, with Pt-PS scores usually poorer. Almost half the patients would have excluded themselves from a hypothetical clinical trial (Pt-PS >/=2). This requires prospective evaluation.