Novogen pleased by cancer drug results

Trials of Novogen's (ASX:NRT) anti-cancer drug phenoxodiol have shown it significantly delays tumour progression in men suffering from late-stage hormone refractory prostate cancer and produces anti-cancer responses in women with cervical cancer.

Novogen's US subsidiary Marshall Edwards (NASDAQ:MSHL; AIM:MSH) informed the London Stock Exchange's Alternative Investment Market that a long term phase Ib/IIa study in 26 men with metastatic prostate cancer was designed to end after 24 weeks of treatment with phenoxodiol, but the unexpected survival of some patients meant that the trial was extended to its current 90 weeks. The study was presented at the International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia.

"The anti-tumour effects of phenoxidiol that is being demonstrated and the lack of side effects are encouraging patients to stay on therapy," said Novogen managing director Chris Naughton.

The study aimed to establish the level of anti-cancer effect of phenoxodiol and whether this effect was dose dependent. Patients were administered various oral doses (20, 80, 200 and 400 mg) of phenoxodiol in a monthly treatment cycles of three doses daily for 21 consecutive days followed by 7 days without treatment.

The study found that 10 out of the 14 patients (71.4 per cent) in the top two dosage groups (200 and 400 mg) were still on therapy after six months compared with one out of 12 (8.5 per cent) in the two lowest dosage groups. The length of time that patients in the highest two dosage groups were benefiting from therapy was 47 weeks compared with 15 weeks in the lowest two dosage groups, although this figure did not include the four patients who remained on therapy after 42, 74, 82 and 90 weeks.

Three of the 14 patients in the two highest dosage groups showed a 50 per cent or greater reduction in levels of the prostate cancer blood marker, prostate-specific antigen (PSA). There were no PSA responses in the two lower-dosage groups.

Patients treated for the extended period were able to remain on phenoxodiol without toxicity.

"We're very pleased with the result, as you can imagine. It's a very promising program," said Naughton. "We've always said that we expect the data to speak for itself, and that's what it is beginning to do."

Naughton said that a phase III trial of phenoxodiol is planned for 2006, "following on from this type of program, just adding data and patient numbers."

The next stage of development of phenoxodiol for prostate cancer will be in patients who have failed to respond to both hormone therapy and docetaxel therapy.

"On the basis of this data, we would expect that phenoxodiol would offer these patients a significant survival benefit, but we also will be interested in testing the ability of phenoxodiol to restore sensitivity to docetaxel in these end-stage patients," said Marshall Edwards chairman Prof Graham Kelly in a statement.

Enrolment in this next study is planned to start in 2006 and will be in the US.

Cervical cancer

At the same conference, Yale University's School of Medicine researchers presented an update on encouraging results from a clinical trial of phenoxodiol in women with early-stage cancer of the cervix and vagina.

So far, the study has recruited 16 women who have been administered 8-hourly doses of phenoxodiol for 21-28 days between their first diagnosis and surgical resection. Of these, 14 have been evaluated with six receiving 50 mg per dose and eight receiving 200 mg per dose.

In the 50 mg dose group, five of six patients (92.8 per cent) had stable disease at surgical resection, and in the 200 mg dose group all eight patients (100 per cent) had stable disease.

Greater levels of the drug were shown to be concentrated in tumour tissues than in the patient's blood and the researchers suggested that deconjugating enzymes (glucuronidase, sulfatase) in the tumours may be converting the drug into a more active form.

If the researchers are correct, said Naughton, then phenoxodiol may be more effective and targeted than previously believed.

Patients are still being recruited to evaluate phenoxodiol at a higher dose of 400 mg.

From the results of recent trials, Naughton said than phenoxodiol appears to be dose dependent, with 400 mg appearing to be the most effective dose.

"This is about the most effective dose, and we think we're pretty close," said Naughton.

Both trials were mono-therapy and used oral formulations of phenoxodiol. "As a chemo drug, giving oral treatment is much more user friendly," said Naughton.