Clinical benefits and risks of phase I oncology trials: experience from a single institution

Abstract

6572 Background: The majority of published series of phase I oncology trials has reported response rates between 4 to 6 percent. A recent meta-analysis of phase I studies showed a higher response rate of 10.6%. Few reports on single-institution phase I experience have been published. Methods: Results from phase I trials conducted at our institution from 1999 to 2007 were reviewed. Data including clinical responses to treatment, toxic events, and treatment-related deaths were recorded. Results: Data from 33 phase I studies [cytotoxic agents (50%), biologic agents (40%), and both (10%)] involving 491 patients (pts) were analyzed. Primary diagnoses included colorectal (25%), ovarian (20%), breast (8.5%), and lung (7%) cancer. 391 pts were assessable for response and the overall response rate (RR) was 8.2% (complete response rate of 1.5%). Patients with documented response had a lower baseline LDH (234 vs 342 U/l, p=0.04), platelet count (167,000 vs 209,000/μl, p=0.03) and serum protein (6.97 vs 7.23 gm/dl, p=0.06) than patients with stable or progressive disease. Notably, patients with a response had a lower mean CTC pain grade while on study (1.1 vs 1.45, p=0.08) than patients with lack of response. Seven of the 32 responses (22%) were observed below the maximum tolerated dose. The rate of stable disease was 39.4%. The mean and median duration on study were 79 days and 53 days, respectively. The treatment-related mortality rate was 1.2%. The rates of hematologic and non-hematologic grade 4 toxic events were 16.7% and 4.3%, respectively. Conclusions: This is one of the largest single-institution series of phase I oncology trials. Our response rate of 8.2% is comparable to that reported in a recently published multi- institution series. This RR falls within the 95% confidence interval of the RR of a majority of third line (and greater) chemotherapy for solid malignancy, and the concept of phase I studies as being ‘non-therapeutic‘ is called into question. No significant financial relationships to disclose.