The ASCO conference presented those attending with an opportunity to find out the latest results from several significant, UK-based, clinical trials from which mature data are now emerging. These included the ICON3, QUASAR and TE20 studies.
Updated results from this large (2,074 patients) randomised comparison of paclitaxel plus carboplatin versus single-agent carboplatin or CAP (cyclophosphamide, doxorubicin and cisplatin) in chemotherapy naïve women with ovarian cancer were as controversial as the preliminary data presented at last year's meeting (PJ, June 5, 1999, p817).
A total of 1,293 trial entrants have now died or experienced disease progression after a median follow-up time of 29 months. The median progression-free survival was 16.2 months for women in the control arm compared with 16.8 months for those receiving paclitaxel plus carboplatin. This difference was not statistically significant, nor was the 2 per cent increase in two-year survival seen for patients on the test arm. Exploratory analysis did not reveal a benefit or disbenefit to any particular sub-group of patients associated with randomisation to either standard or experimental treatment.
These findings allowed Dr N. Colombo (Italy), presenting these results on behalf of the ICON3 collaborators, to conclude that in the three years from treatment randomisation, the ICON3 study had failed to demonstrate the superiority of platinum plus paclitaxel treatment over conventional platinum regimens that was seen in large North American-based studies, such as GOG-111.
She conceded that this might be due to an unusually good performance by the control treatments used in ICON3, rather than a failure of the paclitaxel/platinum combination to behave as expected.
The QUASAR study of adjuvant chemotherapy following surgery for colorectal cancer which recruited 4,927 patients between May, 1994, and October, 1997, included multiple randomisations and investigator choices with a view to answering several questions simultaneously. To date, it has already shown that levamisole adds nothing except toxicity to 5-fluorouracil (5-FU)-based chemotherapy and that high doses of folinic acid (FA) are no better than low doses in potentiating 5-FU in this situation. At the ASCO meeting, a poster presentation by Professor David Kerr (Birmingham, UK) and colleagues, on behalf of the QUASAR group, gave further information on the impact of treatment scheduling on outcome.
All patients entering QUASAR received 30 intravenous bolus doses of 5-FU plus FA. Investigators were at liberty to choose a conventional schedule, in which treatment was given on five consecutive days every month for six months, or a weekly protocol, under which patients were treated on one day each week for 30 weeks. The data reported in New Orleans showed these two schedules to be equivalent in terms of efficacy - three-year survival was 70.3 per cent and 70.8 per cent for the weekly and monthly treatments, respectively, and recurrence rates were, respectively, 36.2 per cent and 35.2 per cent.
However, diarrhoea, stomatitis, neutropenia and skin toxicity were all significantly less common in patients receiving weekly chemotherapy. This lower toxicity was reflected in the reduced frequency of dose reductions necessary for patients following the weekly schedule - 17 per cent were dose-reduced compared with 42 per cent of those on the monthly schedule.
The investigators concluded that by giving 5-FU plus FA weekly, instead of monthly, treatment toxicity could be reduced without compromising efficacy, with the caveat that the two schedules should, ideally, be tested in a prospectively randomised trial.
Because current treatments for testicular cancer are generally very effective, the focus of clinical trials in this area is often to determine the extent to which treatment can be attenuated in order to minimise acute and long-term side effects while preserving anti-tumour efficacy. The TE20 study, which is run jointly by UK Medical Research Council and the European cancer research organisation (the EORTC), incorporated a double randomisation to answer two questions about the chemotherapy of good prognosis testicular germ cell tumours: first, whether three cycles of combination chemotherapy with the BEP (bleomycin, etoposide and cisplatin) regimen is as effective as three cycles of BEP plus one cycle of EP (etoposide plus cisplatin) and, secondly, whether delivery of BEP over three days is as effective as the same treatment given according to the conventional five-day schedule.
Final results of this study were presented in New Orleans by Dr R. de Wit (Brussels, Belgium) on behalf of the investigators who have enrolled 812 patients into the trial. He explained that with this number of entrants the study had sufficient statistical power to detect a 5 per cent difference in two year progression-free survival between study arms, but that no differences were detected, with two-year survivals of 90.4 per cent and 89.4 per cent in the 3BEP and 3BEP+1EP arms, respectively.
Similarly, he reported that three-day BEP was of equivalent efficacy to the five-day regimen, though the contracted treatment schedule did result in greater haematological toxicity.
Dr Summerhayes is principal oncology pharmacist,Guy's and St Thomas's hospitals NHS trust. He attended the ASCO meeting as a guest of Roche Products