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Single Agent Carboplatin

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Single Agent Carboplatin For First-Line Ovarian Cancer

Single-agent carboplatin is acceptable as first-line chemotherapy for ovarian cancer, with its superior toxicity profile and equivalent survival benefit compared with other regimens, according to the results of a randomized trial reported in the August 17, 2002 issue of The Lancet.

The International Collaborative Ovarian Neoplasm (ICON) group reports the results of the ICON3 trial in which 2074 women with ovarian cancer were randomly assigned to treatment with paclitaxel plus carboplatin or to a control group.

Women in the control group received a combination of three drugs or single-agent carboplatin. The drug combination consisted of cyclophosphamide, doxorubicin and cisplatin (CAP). During a follow-up period with a median of 51 months, the researchers looked for overall survival, progression-free survival and toxicity.

Over the follow-up period, 1265 women died. According to an analysis of survival curves, there was no difference in overall survival between women receiving paclitaxel plus carboplatin and CAP or single-agent carboplatin (hazard ratio 0.98, p = 0.74 and hazard ratio 0.99, p = 0.94, respectively).

The median survival time for women receiving paclitaxel and carboplatin was 36.1 months, compared with 35.4 months for women in the control group.

For the 1538 women whose diseased progressed or who died, Kaplan-Meier curves showed no significant difference between the treatment groups (hazard ratio 0.93, p = 0.16), the researchers report.

Among women in the paclitaxel plus carboplatin group, median progression-free survival was 17.3 months, compared with 16.1 months among women in the control group, they add.

Patients receiving paclitaxel and carboplatin had more occurrences of alopecia, fever, and sensory neuropathy than patients receiving carboplatin alone and more sensory neuropathy than women receiving CAP. Women receiving CAP had more fever than women receiving paclitaxel and carboplatin, the ICON team found.

"The results of ICON3 suggest that, up to 5 years from treatment, single-agent carboplatin, CAP, and paclitaxel plus carboplatin are all safe and show similar effectiveness as first-line treatments for women requiring chemotherapy for ovarian cancer," Dr. Peter Harper, leader of the ICON group, from Guy's Hospital, London, said in a statement. "Of these three treatments, carboplatin might be regarded as the preferred treatment because of its better toxicity profile."

Another study has shown that "patients value survival more highly than the quality of life during chemotherapy," Dr. Martin H. N. Tattersall from the University of Sydney, Australia, notes in a related editorial. Yet "the proportion of women with advanced ovarian cancer who have a normal life expectancy remains low despite claims of major progress in treatment in the past few years," he adds.

SOURCE: Lancet 2002;360:500-501, 505-515.

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Based on clinical trials, results showing no difference between single agent platinums (cisplatin or carboplatin) versus platinum/Taxol (GOG Trial # 132, ICON3), the British National Institute for Clinical Excellence (NICE) determined that platinum/Taxol should no longer be considered as standard therapy, and that a range of therapies are equally acceptable.

In the USA, where the administration of platinum/Taxol has been much more profitable to the treating oncologist than single agent platinum, there has been the dogged insistance that platinum/Taxol remains standard, despite clear lack of support for this position, based on the entirety of the clinical trials literature.

The ICON-4 trial took patients who relapsed with so-called "platinum sensitive" disease (relapse > 6 months following last chemotherapy). They were randomized between platinum/taxol and single agent platinum. More than 80% of the platinum/taxol group got carboplatin (as opposed to cisplatin). These all got carbo at a dose of 5 (AUC), which was the same dose given to the single agent platinum group.

Also, a lot of the patients had been treated with single agent platinum as first line therapy. The advantage of the combination was modest (10% improvement in progression free survival at one year). Plus, the combination group got more intense therapy (same dose of carbo plus the addition of another drug). Plus, a lot of the patients were "seeing" Taxol for the first time.

The problem with this study is the complete irrelevance to the question of first line therapy. This question has been asked and answered. Twice. GOG-132 and ICON-3. Platinum-Taxol is NOT superior to single agent carboplatin and single agent cisplatin.

Previously-untreated patients with poorly-differentiated tumors should be treated with single agent carboplatin, while patients with moderate (or moderate-well) differentiated tumors should be treated with a regimen which includes one or more non-platinum drugs.

There is a clear relationship between platinum resistance and tumor differentiaion. Poorly-differentiated tumors are, on average, significantly more sensitive to platinums than are well-differentiated tumors. In contrast, taxol resistance is not related to tumor differentiation. Single-agent platinum may be the most appropriate first-line chemotherapy for poorly-differentiated tumorw, while platinum/taxol may be more appropriate for well-differentiated tumors.

Human Tumor Assay Journal

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

The largest ever international clinical trial of treatments for ovarian cancer, has concluded that standard initial chemotherapy drug treatments for women with ovarian cancer are equally as effective adding the drug paclitaxel (Taxol) to those treatments, and also cause fewer side effects. The surprise finding was published in the August 17 2002 edition of The Lancet.

Treating women who have ovarian cancer initially with standard chemotherapy drugs is as effective as adding the drug paclitaxel (Taxol) to those treatments and causes fewer side-effects.

Ovarian cancer is the fourth most common form of cancer in UK women after breast, bowel and lung cancer. Approximately 6,000 new cases are diagnosed in the UK each year, and 165,000 per year world-wide. The disease is normally treated with surgery followed by chemotherapy. The MRC is currently funding a number of trials in ovarian cancer, aimed at improving the detection and treatment of the disease.

2074 women, from 130 clinical centres in eight countries participated in the MRC funded trial which ran between February 1995 and October 1998. Bristol Myers Squibb provided Taxol at reduced cost for women in the trial and financial support to the co-ordinating centres.

Women were randomly assigned to be treated with standard drugs - carboplatin or a combination of cisplatin, doxorubicin and cyclophosphamide, known as CAP, - or a combination of paclitaxel and carboplatin. The women were followed up after treatment for an average of over four years.

Women who received the paclitaxel/carboplatin combination and those who received carboplatin or CAP all survived their cancer for an average of three years after treatment. Women who received the paclitaxel/carboplatin combination were more likely to suffer hair loss, fever, and numbness and ‘pins and needles’ in their hands and feet - the already known side-effects of paclitaxel.

The study’s results suggest that, for initial treatment of women with ovarian cancer, widely used standard drugs are equally as effective as treatments that include paclitaxel and, on balance, standard treatments such as carboplatin may be considered the preferred treatment as they have fewer side effects.

Dr Peter Harper, a consultant medical oncologist at Guy’s Hospital in London, and Dr Nicoletta Colombo, Associate Professor in Obstetrics and Gynaecology at the European Institute of Oncology in Milan, led the trial, which was co-ordinated by the MRC Clinical Trials Unit.

Dr Harper said: “It’s disappointing that the addition of paclitaxel to the European standard treatment didn’t lead to the great improvement in survival we’d hoped for. The good news is that the survival of all the women in the trial was by all international standards considered the best that is achievable at the moment.

“The results of the trial don’t mean that paclitaxel has no role in the treatment of ovarian cancer, but they do allow doctors and women to have choices according to each individual’s needs. The results also open the door to future treatments allowing paclitaxel to be added in different ways that are not just part of the very first treatment a woman receives.”

Medical Research Council

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