Recent reports
What does ICON 3 mean for women with ovarian cancer?
The ICON 3 report, which appeared in the Lancet on 17th August, raised some interesting and important questions about the treatment of women with advanced ovarian cancer. Dr Helena Earl of the Department of Oncology, University of Cambridge, gives us her view on what conclusions may safely be drawn from the study results.
Unfortunately, the ICON 3 press release reported a very simple statement that ‘single agent carboplatin is equivalent in outcome when used first line to the carboplatin/paclitaxel combination, and is less toxic . This is not, in my view, an appropriate interpretation of the results of the trial. To set ICON 3 in context, two large trials - COG 111(410 patients) and the Intergroup Study OV1O (680 patients) - already show median survival advantages of 14 and 10 months respectively (highly statistically significant) when paclitaxel is added to platinum in first line therapy COG 111 entry was restricted to patients with high-risk stage 3 and 4 disease who had been suboptimally debulked. OV1O did include some high-risk stage 2 patients, but neither study included the lower risk patients who were part of ICON 3.
If the analysis of outcome in ICON 3 is restricted to stage 3 and 4 patients with >2 cm residual bulk disease (i.e. a similar patient group to COG 111), a difference emerges in favour of paclitaxel/carboplatin (although not quite statistically significant). If we combine the ICON 3 results with COG 111 and OV1O results, ICON 3 will contribute evidence for the benefit of paclitaxel with carboplatin first-line in this poor risk group.
Although ICON 3 included 2074 patients and is the largest ever chemotherapy trial in ovarian cancer, it is important to remember that the randomisation was 2:1. For every patient who received the paclitaxel/carboplatin combination, two patients received the control arm. This means that only 700 women received paclitaxel/carboplatin, and more importantly only 331 were in the subgroup with >2 cm residual bulk disease. There were not as many patients in this all-important subgroup as in the other two informative and positive trials.
Given that there is a trend towards an effect in ICON 3, I believe that the conclusion from all three trials taken together can only be that there is a beneficial effect for first-line combinations of carboplatin/paclitaxel in women with so-called bulky disease. The report suggests that COG 1 32 results support the statement about single agent platinum. I do not agree. COG 1 32 should be viewed as a sequential study, since so many patients received both drugs as part of first-line therapy Women starting with paclitaxel often received cisplatin because of lower response rates to single agent paclitaxel therapy, and those given cisplatin were often switched to paclitaxel before progression in the belief that it would benefit them. All that can be reasonably concluded from the COG 132 study is that the survival outcome was the same whether women received sequential mono-therapy (with either cisplatin or paclitaxel first), or combined therapy first-line in women stage 3 and 4 ovarian cancer. How could the press release be at odds with this result? Simply, ICON 3 was effectively a trial for all comers - women with ovarian cancer for whom the doctor and patient were uncertain whether paclitaxel would add benefit to the use of standard treatment. The analysis includes women at all stages of ovarian cancer. It may well be that there is no advantage from adding paclitaxel for women with early disease and that including these women diluted the result so that no benefit was seen.
I believe that we will be justly criticised by the rest of the world if we deny our women with higher risk ovarian cancer access to combined first line therapy because of the ICON 3 data. Given our aims in the UK to deliver improvements in cancer survival rates to approach outcomes already achieved in the rest of continental Europe by 2005, it would be a truly backward step to withdraw a treatment proved to be effective. For me, a more plausible explanation of the data is that ICON 3 contributes to evidence for a definite advantage of platinum/paclitaxel therapy in women with advanced ovarian cancer than that both the US and the Intergroup studies got it absolutely wrong.
Participants invited for research project. I am currently in my final year of an MSc in Counselling and Psychotherapy as a Means to Health at the University of Surrey. My research study is ‘Women's Experience of Ovarian Cancer.
If you would like to take part in this study, please contact Frances Hodges for further details at Kew Moorings, Hilltop Walk, Woldingham, Surrey CR3 7LC
Tel. 01883 652151
The stored embryo dilemma
There's been a lot of press coverage recently about the fate of embryos produced by IVF and stored for future use by couples who later separate and cannot agree. The issues are well discussed in the two articles we reproduce below. What a problem this presents! I suspect that in the Evans/Johnson case, the judge will have to rule against Miss Evans. But what has emerged from this case is that in future IVF clinics will have to store frozen eggs and sperm separately.
It is only when you allow yourself time to consider these moral dilemmas that you realise how society s values have changed over the last decade.
What's your opinion? Please write in and let us know
A historic legal battle
Richard Price, Beezy Marsh and David Wilkes writing in the Daily Mail
Embryos frozen before treatment
A woman is to fight a historic legal battle to safeguard her only chance of motherhood after her fiancée told an IVF clinic to destroy embryos they had created together. Natalie Evans last year received fertility treatment to produce the embryos with Howard Johnston, 25, after she was told that her ovaries had be removed because of ovarian cancer.
When the relationship broke down Mr Johnston contacted the IVF clinic asking them to destroy the frozen embryos. Miss Evans, whose only hope of bearing her own children is now under threat, said, "she would fight to the death for the right to use the embryos."
The inevitable result of treating babies like commodities
Critics of IVF said the battle was the inevitable result of treating babies like commodities. The law governing fertility clinics states both partners must consent before treatment can go ahead. If either partner withdraws permission, clinics are legally obliged to discard frozen embryos under the 1990 Human Fertilisation and Embryology Act. Miss Evans said: "when I received a letter from the clinic saying he wanted the embryos destroyed I was devastated, my world just fell apart. All I've ever wanted is to be a wife and mother, I don't want fast cars and houses, I just want to settle down and have children.
The couple met in 1999 and tried to have children for eighteen months. When they were unsuccessful Miss Evans went for medical tests - only to be told that she had ovarian cancer. "When we found out that I would have to have my ovaries removed, Howard couldn't have been more supportive." But seven months later Mr Johnston walked away from the relationship saying he needed to find himself, she claimed.
I will fight him to the death to stop this from happening" "Since we split up he has turned into a different person. Now it seems he is deliberately wrecking my hope of motherhood - I will fight him to the death to stop that from happening." Miss Evans has promised not to name Mr Johnston as the child s father or to ask for maintenance.
When the morality of test tube babies goes under the microscope
Kirsty Milne writing in Scotland on Sunday
Who would be a judge? It's not all stern sentencing and post-prandial snoozing up there on the bench. Some of society's toughest moral dilemmas are laid at their lordships door. In the High Court in London this week, Dame Elizabeth Butler-Sloss will be asked to rule in the case of two women who want to use frozen embryos to have a baby, but whose partners are trying to stop them. The case is as sad as it is difficult. The embryos were created as a result of in vitro fertilisation (IVF). For Natalie Evans, 30, and her fiancée Howard Johnston, this was a precaution against treatment for ovarian cancer, which left her infertile.
No stranger to issues where ethics and technology collide
Dame Elizabeth is no stranger to issues where ethics and technology collide; recently she left the courtroom to sit by the bedside of the terminally ill Miss B, who claimed the right to refuse treatment. But she will need the judgement of Solomon to resolve this dispute. Miss Evans feels she is waging a battle for custody of her unborn child. The father argues that the embryos are the product of a partnership which is now over.
A woman's longing for a baby
It is an emotive subject putting a woman s longing for a baby against her ex-partner's desire for a say in whether a child of his should be born. At the hearing Miss Evan's lawyer will claim that the law is unfair and discriminates against her. If Miss Evans had been able to conceive naturally he will argue, she could have become pregnant at the time of the break-up and Mr Johnston could have done nothing to stop her. It is only her infertility which gives Miss Evan's ex-partner a right of veto. As this tug of war reveals, the test tube is a great leveller. In the laboratory egg and sperm are equal. IVF knocks out the biological advantage that allows a woman to get pregnant against her partner s wishes or even without his knowledge. That advantage also gives the woman the upper hand in a court of law, she can end the pregnancy without his consent, as a series of legal challenges have shown.
Assisted reproduction is tied to the principle of partnership
IVF changes the balance of power. Both putative (reputed) parents must give permission for embryos to be stored and either can withdraw their consent - as Mr Johnston has done. The law bucks the trend for women to ‘go it alone by insisting that assisted reproduction, unlike natural reproduction, should be tied to the principle of partnership. If Mr Johnston is determined to withdraw his consent, the embryos will be destroyed. Miss Evans argues that her chance to have children will be lost along with the embryos, infringing her right to found a family - as embodied in human rights law. That would not be true if the eggs and sperm had been frozen separately, giving women the opportunity of trying again with another partner.
Fertilised embryos - already exist
What makes the case troubling is that fertilised embryos - just a few cells at this stage - already exist. Even though embryos have no legal rights, some people may feel that it is wrong for them to be destroyed in clinics across the country. Some are weeded out as part of an increasingly sophisticated selection process that allows parents to avoid dangerous conditions or inherited diseases. Others are discarded because the legal time limit - there is usually a five-year limit for storage - has expired. Couples are given leaflets warning them about the deadline. A few years ago there was an outcry when more than 3,300 were destroyed because the 900 couples who owned them had moved or did not respond to letters. There was no guarantee that Mr Johnston would marry hisfiancée any more than the average couple with children can promise not to divorce. Just as children are at the mercy of their parents, a ball of fertilised cells is dependent on the shaky good intentions of the adult world.
Ironing out an imbalance between the sexes
It would be a surprise if Dame Elizabeth allowed the women to try for a pregnancy in direct opposition to their partners wishes, but while IVF may be ironing out an existing imbalance between the sexes, it is making parental responsibility more complicated. Just because conception takes place in a laboratory test tube, it is no less emotionally fraught for the couple concerned and no less morally taxing for the rest of us.
