Survival of 1,181 patients in a phase I clinic: the MD Anderson Clinical Center for targeted therapy experience

Abstract

Purpose: To determine whether the Royal Marsden Hospital (RMH; London, UK) prognostic score for phase I patients can be validated in a large group of individuals seen in a different center and whether other prognostic variables are also relevant, we present an analysis of 1,181 patients treated in the MD Anderson Cancer Center (MDACC; Houston, TX) phase I clinic.

Experimental design: Medical records of 1,181 consecutive patients who were treated on at least one trial in the phase I clinic were reviewed.

Results: The median age was 58 years and 50% were women. The median number of prior therapies was four and median survival 10 months [95% confidence interval (CI), 9.1-10.9 months]. Independent factors that predicted shorter survival in a multivariate Cox model and could be internally validated included RMH score of >1 (P < 0.0001; albumin <3.5 g/dL; lactate dehydrogenase >upper limit of normal, and >two sites of metastases), gastrointestinal tumor type (P < 0.0001), and Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.0004). The median survival was 24.0, 15.2, 8.4, 6.2, and 4.1 months for patients with 0, 1, 2, 3, and 4 or 5 of the above risk factors, respectively.

Conclusion: The RMH score was validated in a large group of patients at MDACC. Internal validation of the independent prognostic factors for survival led to the development of the MDACC prognostic score, a modification of the RMH score that strengthens it.

Fig 1A

Patients by tumor type (total n=1,181).

Fig 1B

Type of Phase I trial.

Fig 2A

Kaplan - Meier survival curve for overall survival in 1,181 patients. Ticks represent patients still alive and hence censored at last follow up.

Fig 2B

Kaplan - Meier survival curve for the 5 risk groups based on MDACC score (n=1,153 patients for whom all baseline data points were available). Ticks represent patients still alive and hence censored at last follow up.

Fig 2C

Kaplan - Meier survival curve for the 4 risk groups based on RMH score (n=1,169 patients for whom all baseline data points were available). Ticks represent patients still alive and hence censored at last follow up.

Fig 3

Proposed algorithm to assign patients to one of the five risk groups that predict survival characterized by summing the number of risk factors present at the time of first visit to the Phase I clinic. All risk factors carry equal weight.