Background Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted. Methods We enrolled 750 patients with previously untreated, metastatic renal-cell carcinoma in a multicenter, randomized, phase 3 trial to receive either repeated 6-week cycles of sunitinib (at a dose of 50 mg given orally once daily for 4 weeks, followed by 2 weeks without treatment) or interferon alfa (at a dose of 9 MU given subcutaneously three times weekly). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, patient-reported outcomes, and safety. Results The median progression-free survival was significantly longer in the sunitinib group (11 months) than in the interferon alfa group (5 months), corresponding to a hazard ratio of 0.42 (95% confidence interval, 0.32 to 0.54; P<0.001). Sunitinib was also associated with a higher objective response rate than was interferon alfa (31% vs. 6%, P<0.001). The proportion of patients with grade 3 or 4 treatment-related fatigue was significantly higher in the group treated with interferon alfa, whereas diarrhea was more frequent in the sunitinib group (P<0.05). Patients in the sunitinib group reported a significantly better quality of life than did patients in the interferon alfa group (P<0.001). Conclusions Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa (ClinicalTrials.gov numbers, NCT00098657 and NCT00083889).

/pdf/sunitinib-versus-interferon-alfa-in-metastatic-renal-cell-1l4etdht18.pdf

Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.

Background.Pediatric patients' self-report of health-related quality of life (HRQOL) has emerged as an important patient-based health outcome. A practical, validated generic measure of HRQOL facilitates assessing risk, tracking health status, and measuring treatment outcomes in pediatric populations

The PedsQL: measurement model for the pediatric quality of life inventory.

ContextMore persons in the United States die from non–small cell lung
cancer (NSCLC) than from breast, colorectal, and prostate cancer combined.
In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors
that express the epidermal growth factor receptor (EGFR), a mediator of cell
signaling, and phase 1 trials have demonstrated that a fraction of patients
with NSCLC progressing after chemotherapy experience both a decrease in lung
cancer symptoms and radiographic tumor shrinkages with gefitinib.ObjectiveTo assess differences in symptomatic and radiographic response among
patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Design, Setting, and PatientsDouble-blind, randomized phase 2 trial conducted from November 2000
to April 2001 in 30 US academic and community oncology centers. Patients (N
= 221) had either stage IIIB or IV NSCLC for which they had received at least
2 chemotherapy regimens.InterventionDaily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib
tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching
placebo).Main Outcome MeasuresImprovement of NSCLC symptoms (2-point or greater increase in score
on the summed lung cancer subscale of the Functional Assessment of Cancer
Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion
size on imaging studies).ResultsOf 221 patients enrolled, 216 received gefitinib as randomized. Symptoms
of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients
receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving
500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial
radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving
250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg.
Symptoms improved in 96% of patients with partial radiographic responses.
The overall survival at 1 year was 25%. There were no significant differences
between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P =
.54). The 500-mg dose was associated more frequently with transient acne-like
rash (P = .04) and diarrhea (P = .006).ConclusionsGefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved
disease-related symptoms and induced radiographic tumor regressions in patients
with NSCLC persisting after chemotherapy.

https://jamanetwork.com/journals/jama/articlepdf/197532/JOC31026.pdf

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients with Non-Small Cell Lung Cancer: A Randomized Trial

Results Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P=.26), radiographic tumor regression (P=.51), and projected 1-year survival (P=.54). The 500-mg dose was associated more frequently with transient acne-like rash (P=.04) and diarrhea (P=.006). Conclusions Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non-Small Cell Lung Cancer

background This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. methods We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression. results Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The oneyear survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone. conclusions Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa043445

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

PURPOSEWe developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale.METHODS AND RESULTSThe five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The ...

E Linn

Papers

The Functional Assessment of Cancer Therapy scale: development and validation of the general measure.