Original Guideline: September 2001
After reviewing the first draft of the guideline report, there was consensus among the Disease Site Group (DSG) members that randomized trials have demonstrated a survival advantage for paclitaxel plus platinum as first-line treatment for ovarian cancer. Other issues addressed in discussion of the guideline included single-agent versus combination chemotherapy, carboplatin versus cisplatin, the preferred doses for paclitaxel, carboplatin, and cisplatin, the appropriate duration of the paclitaxel infusion, the number of cycles of treatment, the addition of anthracyclines to first-line treatment, and the role of intraperitoneal therapy. For some of these issues, only indirect evidence from trials conducted before the introduction of paclitaxel is available, and direct evidence from trials with paclitaxel is emerging. The DSG suggested that more detailed descriptions of data on adverse effects and quality of life from randomized controlled trials (RCTs) should be added to the guideline report for the next draft. Recommendations suggested by the DSG members at the meeting where the first draft was discussed included:
- Carboplatin plus paclitaxel should be the standard treatment for stage II–IV ovarian cancer.
- Carboplatin may be given in doses ranging from area under the curve (AUC) of 5–6.
- Paclitaxel may be used in doses ranging from 135 to 175 mg/m2 given over 3 to 24 hours.
- Intraperitoneal cisplatin plus intravenous paclitaxel is a reasonable treatment option for patients with stage III optimal disease.
- The use of carboplatin as a single agent seems a reasonable alternative for women in whom one wants to minimize toxicity. This is particularly relevant for elderly and medically infirm patients.
The DSG decided to expand the target population for the guideline to include women with fallopian tube and primary peritoneal cancers.
During the subsequent development of the guideline report, the DSG refined several of their original conclusions and recommendations.
- They considered the rationale for recommending carboplatin over cisplatin. While there is no convincing evidence of the superiority of carboplatin over cisplatin in terms of survival, in the opinion of the DSG, the hematologic toxicity imposed by carboplatin is qualitatively preferable to the gastrointestinal and neurologic toxicity imposed by cisplatin.
- Although the evidence is indirect, randomized trials comparing paclitaxel administered at a dose of 175 mg/m2 over three hours with a dose of 135 mg/m2 over 24 hours did not detect a survival difference between these two regimens. It has therefore become common practice to use a three-hour infusion of paclitaxel due to its convenience. The Disease Site Group recommends that paclitaxel be administered as a three-hour infusion at a dose of either 135 to 175 mg/m2.
- No recommendation was made about intraperitoneal chemotherapy. Given the fact that only one study has demonstrated a statistically significant survival benefit for intraperitoneal chemotherapy, it is difficult to consider it as standard therapy or to recommend its use at this time.
- Because of the limited evidence available, the DSG did not include the use of anthracyclines in first-line therapy in the recommendations. As the addition of doxorubicin increases toxicity, and the magnitude of the survival benefit is unclear, the DSG does not recommend the incorporation of anthracyclines as part of first line therapy at the present time. It is hoped that this issue will be clarified by several of the ongoing trials listed in the original guideline document.
- Although there are no randomized trials of chemotherapy in fallopian tube cancer or primary peritoneal cancer, given that most clinicians treat women with these uncommon cancers as they would patients with ovarian cancer, the DSG felt that the recommendations for ovarian cancer could be applied to fallopian tube and primary peritoneal cancer.
A revised draft of the practice-guideline report was reviewed by the DSG in November 2000 and approved for distribution to practitioners in Ontario for their feedback. In April 2001, following the practitioner feedback survey, the DSG reviewed the status of the International Collaborative Ovarian Neoplasm Study (ICON3) trial. Full results of this RCT, which will provide evidence on carboplatin alone versus carboplatin plus paclitaxel, have yet to be published. The ICON3 study was conducted in Europe using a different staging system and with general surgeons performing surgery for ovarian cancer. When the study results are published, the DSG will review them, assess their generalizability to the Ontario setting and update the guideline report.
June 2004 Update
In November 2002, the Gynecology DSG met to discuss the results of the ICON3 trial. The DSG decided to modify the recommendation of carboplatin plus paclitaxel to carboplatin with or without paclitaxel because the results of the ICON3 trial detected that there was no difference in survival between the three treatment groups: paclitaxel plus carboplatin; carboplatin alone; and cyclophosphamide, doxorubicin, and cisplatin.
In June 2004, the Gynecology Cancer DSG met to discuss the results of the SCOTROC trial which compared paclitaxel and carboplatin to docetaxel and carboplatin. The DSG concluded that, based on the results of the trial that indicate that there is no significant survival difference between the two treatments, that either is acceptable. The DSG acknowledged that there was a significant difference in the toxicity between the treatment arms: significantly more neurotoxicity among women treated with paclitaxel than docetaxel; however, there was significantly more myelosuppression among the women treated with docetaxel than paclitaxel.
