Both reports confirmed the superiority of the experimental arm, but some perplexities do remain, for either the choice of the control arm (low doses of prednisone are not universally accepted as the standard palliative treatment in hormone-resistant prostate cancer), or the rapid approval by regulators on the basis of the data of the first paper.
The first point is the choice of the control arm.
Regarding the choice of the control arm, we agree that the standard adjuvant treatment for stage III colon cancer since 1990 has been 5-fluorouracil plus leucovorin (5-FU/LV) (NIH, 1990; IMPACT, 1995; Wolmark et al, 1999).
Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed.
Choice of control is important.
Concern about the choice of CP 750,75) as a control arm in GOG-111 was first raised in 1996 (Parmar and Sandercock, 1996) when the results of this trial were first published, prior to any results being available from the other trials.
Patients in the no treatment arm were reminded of the importance of the control arm.
This study randomized patients to four cycles of FEC, followed by four cycles of docetaxel or a control arm of the physicians' choice: either four cycles of epirubicin followed by four cycles of CMF, or eight cycles of CMF.
Another concerning aspect is the choice of sedation agent in the control arm.
HRQoL was not assessed in the trial due to the variety of treatments and schedules in the control arm (treatment of physician's choice).
It closely followed the glycaemic control achieved in the control arm of NICE-SUGAR enforcing the generalizability of NICE-SUGAR study results to ANZ and justifying the choice of the specific range of glycaemic level apply to the control arm of NICE-SUGAR.
