Australian cancer drug offers hope to patients
By Amy Lawson
November 27, 2005
AUSTRALIAN cancer experts are spearheading the trial of a new drug that is dramatically improving the survival rates of patients with aggressive head and neck cancers.
The drug, which has ramifications for the treatment of other aggressive forms of cancer including those in the lungs, cervix and oesophagus, could be available as soon as the end of next year if given the green light by drug administrators.
Professor Lester Peters, a world leader in cancer research from the Peter MacCallum Cancer Centre in Melbourne, is leading the trial for the drug tirapazamine.
The trial is in its final testing phase and has already had some astounding results.
Sandy Bodecker, the former husband of runner Cathy Freeman, participated in one of the trials.
He made a full recovery from the throat cancer he was originally told was inoperable.
In the first phase of the trial, only two of the 16 patients with advanced head or neck cancers had a recurrence of their tumours after receiving treatment with the drug.
"It can be a cure, but not in everyone," Professor Peters said yesterday in Sydney. "But a huge proportion of patients have had their tumours eradicated if they've been treated with this drug.
"It's a very gruesome way to die - of uncontrolled cancer in the head and neck. If we can prevent that . . . we've done them a service."
Head and neck cancers are almost always found in smokers and are among the most difficult of all cancers to treat. Cure rates for advanced disease are poor and patients often end up with significant disabilities.
Professor Peters said tirapazamine worked by targeting cancer cells that were starved of oxygen, which were typically resistant to conventional treatment and particularly malignant.
The drug is used with chemotherapy and radiation therapy.
"The triple combination has been shown to have a good effect in this advanced form of cancer," Professor Peters said.
Dr Chris Milross, head of Radiation Oncology at Royal Prince Alfred Hospital's Sydney Cancer Centre, said the trials had the potential to change the standard treatment given to patients with head and neck cancers.
"It shows our dedication to groundbreaking research, and also illustrates that our patients have the potential to get the benefit of that leading research," he said.
"It's not a big stretch to imagine the same sorts of principles transferred to other cancers such as lung, cervix and oesophagus."
The second stage of phase three of the trial, involving 550 patients around the world, is under way and should be finished by June.
If the final stage is successful, the drug can then be registered by the US Food and Drug Administration.
Source: The Sun-Herald
smh.com.au
1 of 6 ongoing trials for Tirapazamine
Concomitant Radiation and Cisplatin with and Without Tirapazamine in Treatment of Advanced Head and Neck Cancer
clinicaltrials.gov
Recent Abstract
Experimental and Clinical Therapeutics
Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall
(PP099) Mechanism of sensitization of hypoxic cells to cisplatin by tirapazamine.
Chernikova, Sophia*,1, Peters, Katherine1, Kovacs, Mary1, Brown, J. Martin1, 1 Radiation Oncology, Stanford, CA, USA
ABSTRACT- Tirapazamine (TPZ) is an anticancer drug that under hypoxic conditions is activated into a highly damaging free radical, thus taking advantage of the hypoxic environment of solid tumors. Under hypoxic conditions the TPZ radical generates multiple types of damage to DNA including base damage, single-strand breaks, and double-strand breaks. We and others have previously shown that TPZ has a unique schedule-dependent synergy with cisplatin such that pretreatment with TPZ before cisplatin produces synergistic cell killing, while simultaneous treatment with TPZ and cisplatin leads to only additive cytotoxicity. Despite ample evidence that the TPZ potentiation of cisplatin cytotoxicity in tumors is the result of hypoxia, the nature of the interaction between cisplatin and TPZ is still unclear. However, we have shown that this interaction is absent in CHO UV41 cells deficient in the nucleotide-excision repair (NER) protein, XPF, and that TPZ pretreatment results in decreased (or delayed) repair of interstrand and intrastrand cross-links produced by cisplatin. Taking together these data suggest that the ERCC1/XPF complex, which is the only NER factor required for the repair of DNA interstrand cross-links, is involved in the TPZ potentiation of cisplatin effect. At present we are exploring the hypothesis that the potentiation of cisplatin cytotoxicity by TPZ is due to sequestering of ERCC1/XPF by TPZ-induced damage.
Key words: tirapazamine, hypoxia, cisplatin, ERCC1/XPF
abstracts.co.allenpress.com |
