ZK-Epothilone (ZK-Epo) is a novel chemotherapy drug currently in clinical trials to see if it has an effect against advanced prostate, ovarian and breast cancer. ZK-Epo may work differently than Taxotere and other taxane drugs. It is being tested against all three cancers at centers across the USA and also in Argentina (for ovarian cancer) and Canada (for breast cancer) .

One of the medical centers now recruiting prostate cancer patients for this trial is Oregon Health and Science University (OSHU). The chief clinical investigator for the OSHU trial is Tomasz Beer, MD.

The sponsor for all 3 trials is the company itself, Berlex Inc. Berlex is the US affiliate of Schering AG, headquartered in Berlin, Germany. Berlex’s products include Leukine (Granulocyte macrophage colony-stimulating factor) and Menostar, a brand of estrogen patch.

The full name of this trial for men with advanced prostate cancer is ZK-Epo Given With Prednisone in Patients With Metastatic Androgen-Independent Prostate Cancer. All the centers recruiting patients for this trial are listed at ClinicalTrials.gov and appear below.

How is ZK-Epo expected to work (its mechanism of action) amd what have preclinical studies shown about its effect on cancer cells and tumors implanted in mice? Firstly we have the company’s statements: In their blurb for the prostate cancer trial they say:

• ZK-Epo is a member of the epothilone class which binds to beta-tubulin causing microtubule stabilization. These mechanisms of action leading to tumor cell kill are similar to those of the taxanes (e.g. docetaxel).

• Preclinical models, both in vitro and using animal xenograft systems including several human prostate cancer cell lines have shown ZK-Epo inhibits tumor cell growth at least as well as taxanes.

• ZK-Epo was developed to be insensitive to common mechanisms of cancer chemotherapy resistance effecting drugs such as taxanes. This characteristic of the study drug has been verified in several preclinical models as well as responses seen in patients with solid tumor cancers having been previously exposed to taxanes and tumor types not generally sensitive to taxanes.

• Updated safety information from ongoing phase 2 studies in other cancer types now totaling over 120 patient shows that the toxicities at the dose of ZK-Epo used in this study are lower than previously seen in phase 1 studies with no significant toxicity other than neuropathy which occurs at rates similar to or lower than that of docetaxel.

A technical description of this class of drugs (epithilones) and how they are expected to work is set out in in a 2004 article available online The mechanism of action and biologic activity of epothilones, by Susan Goodin, Michael P. Kane, and Eric H. Rubin at Department of Medicine, Department of Pharmacology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School; and The Cancer Institute of New Jersey, New Brunswick, NJ.

“Drugs that target microtubules are among the most commonly prescribed anticancer therapies,” these authors explain. Taxol (Paclitaxel) and Taxotere (Docetaxel) lead the pack.

“Epothilones have emerged . . . as a new class of microtubule-targeting drugs. ” The epothiliones were discovered as cell-killing (cytotoxic) metabolites from the myxobacterium Sorangium cellulosum (a bacteria found in soil).

Subsequently, epothilones “were identified as microtubule-stabilizing drugs that competitively inhibit binding of paclitaxel to microtubules in vitro. Preclinical studies indicate a relatively broad spectrum of action for epothilones, including activity in paclitaxel-resistant models. Furthermore, promising antitumor activity has been observed in initial clinical trials with several epothilone analogs.”

For men with hormone refractory prostate cancer, Taxotere is widely available as a first-line chemotherapy drug approved by the FDA. You will not be eligible for this ZK-Epo Phase I/II prostate cancer trial if you have already taken Taxotere or any chemotherapy.

Whether the effect of Taxotere might diminish if taken after ZK-Epo is unknown. This is the type of question you might want to bring up with your own oncologist and with the lead oncologist in charge of each trial site (e.g in Oregon, with Dr. Beer).

If ZK-Epo and Taxotere and Taxol work differently enough, one drug could be taken after another to extend the time of a patient’s overall response. But this unknown. Also consider that the one known side effect associated with ZK-Epo, so far, is neuropathy. This a side effect of many other chemos including Taxotere.

Patients who meet any of the following criteria will be excluded:

• Any previous cytotoxic chemotherapy regimen
• Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy
• Herbal medicines (e.g. PC-SPES) within 4 weeks before start of study treatment
• Symptomatic brain metastases requiring whole-brain irradiation
• Active infection
• Time period since prior therapy:
- Prior radiotherapy: (must be longer than) 4 weeks before start of study treatment
- Prior flutamide: (must be longer than) 4 weeks before start of study treatment
- Prior bicalutamide or nilutamide: (must be stopped more than) 6 weeks before start of study treatment
- Prior non-cytotoxic experimental agents: (must be stoppedmore than) 4 weeks before start of study treatment

Centers recruiting for prostate cancer:

California: Fountain Valley; Recruiting

Florida: Sarassota; Recruiting

Montana: Billings; Recruiting

New Mexico: Farmington; Not yet recruiting

Ohio: Canton; Recruiting

Oregon: Portland; Recruiting

Pennsylvania: Altoona; Recruiting

Texas: Fort Worth; Recruiting

Washington: Seattle; Not yet recruiting

Argentina: Córdoba ; Recruiting

Argentina: Buenos Aires; Recruiting

Two more ZK-Epothilone (ZK-Epo) trials are recruiting ovarian and breast cancer patients:

ZK-Epo Given With Carboplatin in Patients With Recurrent Ovarian Cancer .
A Phase I-Phase II clinical trial recruiting patients at centers in Little Rock, Arkansas; Bakersfield, San Diego, California, and Los Angeles, California; Savannah, Georgia; South Bend, Indiana; Baltimore, Maryland; Lebanon, New Hampshire; Oklahoma City, Oklahoma; Roanoke, Virginia and Tacoma, Washington.

Evaluation of a New Agent for Treatment of Advanced Stage Breast Cancer is a Phase II trial recruiting in USA and Canada:
Alaska: Anchorage, Alaska; Recruiting

California: Fountain Valley, Palm Springs, Bakersfield; Recruiting

Colorado: Auroora; Recruiting

District of Columbia: Washington; Recruiting

Florida: Daytona Beach; Recruiting

Illinois: Decatur; Recruiting

Maryland: Baltimore; Recruiting

Minnesota: Minneapolis; Recruiting

New Jersey: Livingston; Recruiting

New York: New York (weill , 10021; Recruiting

New York: Bronx; Recruiting

Oregon: Portland; Recruiting

Pennsylvania: Pittsburgh; Recruiting

Texas: San Antonio; Recruiting

Texas, Houston; Recruiting

Washington: Tacoma; Recruiting

Canada: Quebec, G1S 4L8; Recruiting

Canada: Ontario: Toronto M4N3M5; Recruiting

Canada: Quebec: Montreal H3T 1E2; Recruiting

Canada: Quebec: Greenfield Park, Recruiting