The trial started in 04/00. The mid-point of enrollment was 05/01. PR said that "more than half" were enrolled, with n at that time projected to be 280. So assume 151/302 were enrolled as of 05/01. Clearly enrollment speeded up as the trial progressed (or perhaps more likely things were just slow at the beginning).
If we try to simplify by assuming everyone was enrolled on 5/01, then 28% of patients were alive 2 years later. So everything boils down to what the tail of the distribution looks like assuming no treatment.
This is the eligibility of the study:
Eligibility: 1. Histologically confirmed renal cell carcinoma 2. Measurable and/or evaluable metastatic disease. 3. Progressive disease objectively documented within 12 weeks of the end of the first-line treatment regimen, which has included IL-2 and/or interferon. (The patient has to have failed previous IL-2 or interferon therapy.) 4. At least 1 month but no longer than 6 months since receiving immunotherapy . 5. Life expectancy exceeds 3 months. 6. ECOG performance status of 0 or 1.
Here's what I found on prognosis of metastic disease:
Br J Cancer 2003 Feb 10;88(3):348-53
Links
Metastatic renal carcinoma comprehensive prognostic system.
Atzpodien J, Royston P, Wandert T, Reitz M; DGCIN -- German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group.
medizinische Hochschule Hannover, Germany. SekrProAtzpodien@yahoo.de
The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-alpha 2a (INF-alpha), s.c. interleukin-2 (IL-2) (n=102 pts), (B) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n=235 pts) or (C) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n=88 pts). Kaplan-Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count > or = 6500 cells microl(-1), (4) serum lactate dehydrogenase level (LDH) > or = 220 U l(-1), and (5) serum C-reactive protein level (CRP) > or = 11 mg l(-1). Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio=1.9, P<0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio < or = 1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.
So there clearly is some tail here - the 8 month median survival patients still had a 5% shot at 5-year survival. SO I don't think we can simply assume that the placebo patients are all dead.
Peter |
