Possible New Combination Chemotherapy for Patients with Advanced Prostate Cancer

For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel. For example, docetaxel is commonly used as the "first-line" therapy, while cabazitaxel is used as the "second-line" therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. This week, however, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Center may change the perspective on a role for combination chemotherapy in advanced disease.

 Carboplatin  Cabazitaxel   Docetaxel

The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin -- a type of platinum chemotherapy -- in patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, 160 men have been randomized to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.

To monitor the effects of treatment, MD Anderson researchers tracked several variables including Progression Free Survival, as well as changes in blood levels of prostate-specific antigen (PSA) and bone-specific alkaline phosphatase (BAP, a marker of prostate cancer in bone cells). In addition, safety and toxicity were monitored for both patient groups.

Analysis and comparison of the data demonstrated that median PFS was significantly longer for patients receiving combination versus single agent chemotherapy (6.7 months vs 4.4 months, respectively, p = 0.01). Furthermore, reductions in both PSA and BAP were greater for the combination therapy group. PSA reductions greater than 50 percent occurred 60 percent of the time with combined chemotherapy vs. 44 percent with the single drug. PSA reductions greater than 90 percent occurred 28 percent of the time with two chemotherapy drugs vs. 20 percent with one. In addition, BAP reductions greater than 50 percent for combination vs. single drug were 63 percent and 25 percent respectively.

Side effects, such as fatigue, anemia and neutropenia were comparable for both the single-drug regimen and two-drug regimen. In addition, there were no significant toxicity events.

"We believe cabazitaxel-carboplatin combination chemotherapy may become the clinical standard for advanced prostate cancer once additional safety, efficacy and overall survival data is generated," explained Paul Corn, M.D., Ph.D., an associate professor of genitourinary medical oncology at MD Anderson. "Dr. Ana Aparicio's lab is currently developing tumor-specific biomarkers to identity patients with an aggressive variant of prostate cancer most likely to benefit from this approach."

Possible New Combination Chemotherapy for Patients with Advanced Prostate Cancer 

Positive results from combination drug trial for late-stage ovarian cancer

In continuation of my update on  carboplatin

Researchers from IU Medical Sciences Program-Bloomington  and Indiana University Melvin, have found that, an experimental two-drug combination (decitabine & carboplatin) for treating late-stage ovarian cancer continues to produce strong results, leading its Indiana University researchers to actively pursue the next step, conducting a larger clinical trial to test the therapy and to see how it compares with existing treatments for ovarian cancer.

The researchers have been investigating the addition of decitabine, which is marketed as Dacogen in the United States, because they suspect it reactivates tumor suppression genes that are turned off in ovarian cancer cells and improves cells' susceptibility to anti-cancer drugs like carboplatin.

"The science associated with the trial is novel and exciting and could have impact in the future," she said.....

More...

Two-drug phase I trial shows promise in treating late-stage ovarian cancer

In continuation of my update on carboplatin .....

Researchers from Indiana University School of Medicine, have come up  with interesting finding from a two-Drug Phase I Trial Show, i.e.,  the combination of decitabine (see structure) and carboplatin appears to improve the outcome of women who have late-stage ovarian cancer. Researchers report four of 10 patients who participated in a phase I clinical trial had no disease progression after six months of treatment. One patient experienced complete resolution of tumor tissue for a period of time.

"Carboplatin is the most efficient drug therapy for ovarian cancer,"  unfortunately, patients with recurrent disease become resistant to the drug after one or two rounds claims the lead researcher.."

Decitabine was first used to treat the study patients intravenously daily for five days followed on the eighth day with carboplatin. After a month, the regimen begins again.

Encouraged by the results of the phase I trial, which determined the safety of two different dosing regimens, a phase II trial is now under way with 17 patients already enrolled. Phase II trials are primarily focused on assessing the effectiveness of a drug or treatment protocol.

As per the claim by the researcher, decitabine  (a known methylation inhibitor) can help return tumor suppression genes to an active state, and also improve cells' susceptibility to anti-cancer drugs like carboplatin. Researchers adds that decitabine isn't just targeting active ovarian cancer cells, but also cancer stem cells that seem to survive the first treatments. 

Researchers conclude that, by keeping tumor suppression genes from being methylated, carboplatin and other platinum-based treatments for ovarian cancer have a better chance of success in the late stages.

Ref : http://www3.interscience.wiley.com/journal/123500856/abstract?CRETRY=1&SRETRY=0

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

In continuation of my follow up on cisplatin derivatives, I find this article interesting to share with.....

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

Picoplatin a better drug than oxaliplatin for colorectal cancer !

In one of my earlier blog, I did mention about the Cisplatin (Cisplatin doubles lung cancer survival time in mice !).

About Cis-platin & other drivatives:

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) is a platinum-based chemotherapy drug used to treat various types of cancers, (sarcomas, some carcinomas (small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was the first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA which ultimately triggers apoptosis (programmed cell death).

Now its the turn of Picoplatin [see structure , Amminedichloro(2-methylpyridine)platinium)], Poniard Pharmaceuticals, Inc. has come up with some interesting results from its Phase 2 trial of picoplatin in patients with metastatic colorectal cancer (CRC). Picoplatin, given once every four weeks in combination with 5-fluorouracil and leucovorin in the FOLPI regimen, has comparable efficacy to oxaliplatin, given in combination with 5-fluorouracil and leucovorin in the modified FOLFOX-6 regimen, as a first-line therapy for CRC, as assessed by one-year survival rate, progression-free survival (PFS) and disease control. The company claims that, (from the updated proof-of-concept Phase 2 safety and efficacy results) picoplatin could be superior to oxaliplatin as a neuropathy-sparing alternative when used in combination as a first-line treatment for metastatic colorectal cancer.

Source : http://investor.poniard.com/ReleaseDetail.cfm?ReleaseID=424813.