Advanced Colorectal Cancer: A Meta-Analysis of 13 Trials

This dataset comprises 3089 patients enrolled in 10 historical trials and 1263 patients enrolled in 3 validation trials that all had a fluorouracil + leucovorin group in common (Buyse et al., 2007). Historical trials compared fluorouracil + leucovorin with fluorouracil alone (7 trials, 1744 patients), or fluorouracil + leucovorin with raltitrexed (3 trials, 1345 patients). Validation trials (1263 patients in total) compared fluorouracil + leucovorin with the same + irinotecan (2 trials, 843 patients) or with the same + oxaliplatin (1 trial, 420 patients). The variables collected for every patient randomized in each of these trials consisted of patient identifier, center identifier, randomization date, treatment assigned by randomization, tumor measurability (i.e., measurable or non-measurable tumors), age, gender, performance status, primary tumor site (colon or rectum), site of metastases, overall response status with the first assigned treatment, date of response, date of progression with the first allocated treatment, date of death or last visit, survival status, and cause of death if applicable. The control group (Z = 0) was considered to be fluorouracil + leucovorin in all trials, and the other treatment group was considered experimental (Z = 1). Note that in reality fluorouracil alone was the control group


25 Trials in Advanced Colorectal Cancer. Overview of the variables in the dataset.

Variable name



The trial in which a patient was treated


The identification number of a patient


The treatment indicator, coded as 0=Control and 1=Ex- perimental


Binary response (a candidate surrogate), coded as 0=no response and 1=response


Categorical ordered response (a candidate surrogate), coded as 1=complete response (CR), 2=partial response (PR), 3=stable disease (SD) and 4=progressive disease (PD)


Performance status, a baseline categorical ordered covariate taking the values 0, 1 or 2


Survival time in days (the true endpoint)


Censoring indicator for survival time (0=alive, l=dead)

in the 7 trials that had compared fluorouracil alone with fluorouracil + leu- covorin. The convention adopted here facilitates interpretation in so far as the same control group is used throughout. In the meta-analysis, the experimental group was statistically different from the control group in terms of progression-free survival and survival in both the 10 historical trials and the 3 validation trials.

For the surrogacy analyses (Buyse et al., 2007; Burzykowski et al., 2001), the true endpoint (T) is survival time, calculated from the day of randomization to the day of death irrespective of the cause of death. The candidate surrogate endpoint (S) is progression-free survival, calculated from the time of randomization to progressive disease or death from any cause. Progressive disease is defined as an increase of more than 25% in the tumor surface area measured by CT-scan or the appearance of any new lesion. In historical trials, 1760 patients (57%) progressed or died within 6 months, and 1622 (52%) died within 1 year. Hence the information would be about the same for an analysis of progression-free survival at 6 months as for an analysis of survival at 1 year.

In the remainder of this book, this dataset will be referred to as the Col- orectal13 dataset. The dataset is included in the R library Surrogate (where it can be accessed using the command data (Colorectal13)) and it can be downloaded from (file Colorectal13.txt). Table 2.6 provides an overview of the variables that are included in the Colorectal^ dataset. The data were provided by the Meta-Analysis Group in Cancer, the Biostatistics and Epidemiology Unit of Institut Gustave-Roussy, AstraZeneca, Sanofi-aventis, and Pfizer (see Buyse et al., 2007).


13 Trials in Advanced Colorectal Cancer. Overview of the variables in the dataset.

Variable name



The trial in which a patient was treated


The treatment indicator, coded as 0=Control and 1=Ex-



Progression-free survival in months (the candidate surro-



Censoring indicator for progression-free survival


Survival time in months (the true endpoint)


Censoring indicator for survival time (0=alive, l=dead)

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