PARP Drugs May Be Miracle Cure for Cancer Suggests
Success with Breast, Ovarian, Prostate Cancer
NEJM editorial says PARP inhibitors may point to a
new direction for anticancer drugs
Patricia
Buckles, after 29-year battle with breast cancer, says the
cancer disappeared after treatment with PARP inhibitors. View
the NBC News report by Brian Williams.
Click
here.
June 25, 2009 The battle against cancer seems to
be on the verge of a major step forward, according to a study reported
in the New England Journal of Medicine. The success of a new class of
drugs PARP inhibitors in destroying the disease points to a new
direction in the development of anticancer drugs, says an editorial in
the current NEJM.
These drugs appear to have the ability to
selectively kill cancer cells without harming normal cells and patients
in a clinical trial report few side effects.
The findings of our study provide very promising
evidence that the potent PARP inhibitor olaparib may be useful for
treating BRCA-deficient breast cancers, said Andrew Tutt, MB ChB, PhD,
director of the Breakthrough Breast Cancer Research Unit at Kings
College in London.
However, this drug is in a very early stage of
development, and additional clinical trials are necessary to determine
the best way to use olaparib in women with BRCA-deficient breast cancer.
We are actively discussing the design of future PARP inhibitor studies
for women with BRCA1 and BRCA2 mutations.
Dr. Tutt, whose work was included in the NEJM
report, presented his success with breast cancer patients earlier this
month at the annual meeting of the American Society of Clinical
Oncology.
That small, Phase II international multi-center
study found that more than a third of women with BRCA1 or BRCA2
mutations and advanced breast cancer that persisted despite prior
treatment experienced tumor shrinkage after receiving the
investigational PARP inhibitor olaparib (AZD2281), a novel, potent, oral
PARP inhibitor.
In this study, Dr. Tutt and his colleagues examined
the response rate to olaparib (as evidenced by tumor shrinkage) in 54
women with breast cancer that was deficient in BRCA1 or BRCA2 and that
persisted despite several rounds of standard chemotherapy.
Forty percent of the patients responded to olaparib
(experienced tumor shrinkage) at the higher of the two doses used in the
study.
Olaparib was well tolerated, with the most common
side effects being mild fatigue, nausea and vomiting.
In the NEJM study the researchers treated 60
patients; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a
strong family history of BRCA-associated cancer but declined to undergo
mutational testing.
The olaparib dose and schedule were increased from
10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously.
Reversible dose-limiting toxicity was seen in one of eight patients
receiving 400 mg twice daily (grade 3 mood alteration and fatigue) and
two of five patients receiving 600 mg twice daily (grade 4
thrombocytopenia and grade 3 somnolence).
This led us to enroll another cohort, consisting
only of carriers of a BRCA1 or BRCA2 mutation, to receive olaparib at a
dose of 200 mg twice daily, the authors write.
Objective antitumor activity was reported only in
mutation carriers, all of whom had ovarian, breast, or prostate cancer
and had received multiple treatment regimens, they said.
They concluded that Olaparib has few of the adverse
effects of conventional chemotherapy, inhibits PARP, and has antitumor
activity in cancer associated with the BRCA1 or BRCA2 mutation.
Several individuals that participated in the study
and saw their cancers shrink were interviewed by NBC news for a report
that appeared on the evening news with Brian Williams on June 24.
Background Information:
Inhibition of Poly(ADP-Ribose) Polymerase in
Tumors from BRCA Mutation Carriers (10.1056/NEJMoa0900212) was
published on June 24, 2009, at NEJM.org.
Authors include
Peter C. Fong, M.D., David S. Boss, M.Sc.,
Timothy A. Yap, M.D., Andrew Tutt, M.D., Ph.D., Peijun Wu, Ph.D., Marja
Mergui-Roelvink, M.D., Peter Mortimer, Ph.D., Helen Swaisland, B.Sc.,
Alan Lau, Ph.D., Mark J. O'Connor, Ph.D., Alan Ashworth, Ph.D., James
Carmichael, M.D., Stan B. Kaye, M.D., Jan H.M. Schellens, M.D., Ph.D.,
and Johann S. de Bono, M.D., Ph.D.
Source Information
From the Drug Development Unit, Royal Marsden
National Health Service (NHS) Foundation Trust and the Institute of
Cancer Research, Sutton, Surrey (P.C.F., T.A.Y., S.B.K., J.S.B.); the
Breakthrough Breast Cancer Research Centre at the Institute of Cancer
Research (A.T., P.W., A.A.), and the Breakthrough Breast Cancer Research
Unit at King's College London, Guy's Campus (A.T., P.W.) both in
London; KuDOS Pharmaceuticals, Cambridge (P.M., A.L., M.J.O., J.C.); and
AstraZeneca, Macclesfield (H.S.) all in the United Kingdom; and the
Netherlands Cancer Institute, Amsterdam (D.S.B., M.M.-R., J.H.M.S.); and
Department of Pharmaceutical Sciences, Utrecht University, Utrecht (J.H.M.S.)
both in the Netherlands.
