New Chemo Combo
Posted 4/27/2010
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It is always good to hear about progress in treating breast cancer. Scientists have known for years that it is often more effective to combine several chemotherapy agents (drugs) than to use one at a time. THe non-scientific explanation for that is that each drug has a unique mechanism, killing cancer cells in different ways and different time frames. Using one drug may mean that some cells are resistant and continue to thrive. Using more than one drug may mean that fewer escape.
This is a summary from Med Scape about a novel drug combination used to treat refractory (meaning resistant) breast cancers. This is still a very new idea, only now going to clinical trials. But it is welcome news in the general observation of progress being made--and the hope that this particular idea will turn out to be valuable.
AACR: Novel Combo Therapy May Overcome Resistant Breast Cancer
By Ed Susman, Contributing Writer, MedPage Today
April 26, 2010
Review
WASHINGTON -- A combination therapy comprising trastuzumab (Herceptin) and two investigational agents, pertuzumab (Omnitarg) and an anti-tubulin cytotoxic agent (DM1), was effective against breast tumors refractory to medical treatment in preclinical testing, a researcher said here.
The combination treatment is now in clinical trials, said Carter Fields, a researcher at Genentech in South San Francisco, Calif., who reported data from animal experiments here at the annual meeting of the American Association for Cancer Research.
The company is investigating the effectiveness of a conjugate drug linking trastuzumab with DM1.
Alone, the conjugate appeared to have no efficacy against treatment-refractory breast tumors, but when combined with pertuzumab, an antibody that inhibits dimerization of the HER2 receptor protein, the combination shut off tumor growth. In xenograft models of breast cancer and lung cancer, mice treated with a control vehicle substance,
pertuzumab, the trastuzumab-DM1 conjugate, or a combination of all the active drugs showed that the combination virtually stopped tumors from growing relative to baseline, whereas tumor volume rose significantly in the other arms of the study.
For example, in laboratory animals implanted with MDA-MB-175-V II xenografts, tumor volume at baseline was about 200 mm3 for all the animals. After 35 days, tumor volume in the combination arm was less than at baseline while in the control animals volume reached 1,000 mm3 after 25 days, when the animals were sacrificed; in the pertuzumab monotherapy arm, the tumor volume reached 1,000 mm3 after 35 days, and in the trastuzumab-DM1 monotherapy arm the tumor volume reached about
800 mm3 after 35 days.
"The combination of both agents results in significantly (P<0.05) enhanced antitumor efficacy," Fields told MedPage Today at his poster presentation. In another experiment with laboratory animals exposed to Calu-3 xenografts, tumor growth was again
delayed the longest in patients treated with high-dose combination regimens. In mice exposed to KPL- 4 xenografts, mean tumor volume rose for all mice except those on the high-dose 3mg/kg combination of trastuzumab-DM1 and pertuzumab where researchers reported about an 80% decline in tumor volume from a baseline of about 275 mm3 to around 50 mm3 after 54 days.
Field noted that the effects of the combination lasted long after treatment stopped. The animals received only a baseline combination treatment, followed by two more pertuzumab infusions -- the final one on day 14.
Overall, Field said the experiments showed that the trastuzumab-DM1 and pertuzumab combination:
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