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New Therapies - Watch List

Available Drugs - New Uses for Colon Cancer
New Drugs to Watch for in Future Clinical Trials

Available Drugs - New Uses for Colon Cancer

Tetracycline

11/11/01 Ontario Cancer Centre Hopes to Discover a $1-a-Day Cancer Treatment A team of researchers at the Hamilton Regional Cancer Centre are testing the cancer-fighting ability of tetracyclines, a family of safe and inexpensive acne antibiotics that have been used for decades. Although the research project is focused on breast cancer, and is funded by the Canadian Breast Cancer Research Initiative, the tetracycline project may also prove beneficial for men suffering from Prostate Cancer. The researchers believe tetracyclines can act as a shield for bones, preventing the spread of some types of tumours in a cancer patient
11/11/01 Novel drug starves tumors lifelines SAN FRANCISCO, Feb. 16 - A new form of an old drug shows promise in treating cancer, researchers reported here Friday. In a new study, a modified formulation of the antibiotic tetracycline appeared to starve the lifelines of tumors in patients with the AIDS-related cancer Kaposi's sarcoma

WHILE THE findings are still preliminary, the tetracycline derivative, known as Metastat, completely eradicated cancer in one patient and shrank tumors in another seven, reported Dr. Bruce Dezube of Beth Israel Deaconess Medical Center in Boston. Noting that all but one of 18 patients had failed to respond to any of the potent cancer drugs typically used to treat the disease, Dezube called the work "very exciting." Additionally, modified antibiotics are offering a novel approach for treating not only other cancers but also a host of tissue-destructive diseases ranging from periodontitis and arthritis to diabetes and osteoporosis, researchers said at the annual meeting of the American Association for the Advancement of Science.
11/11/01 Non-Antibiotic Properties of Tetracyclines and Other Antibiotics July 1-6, 2001 Bal Lokeshwar, Ph.D. , University of Miami CMTs and control of metastatic cancer Michelle Rudek , National Cancer Institute Clinical pharmacology of COL-3 in patients with refractory metastatic cancer Sandy Simon, Ph.D. , SUNY Stonybrook Downregulation of the invasive phenotype of tumor cell lines by chemically modified tetracyclines
11/11/01 Altered Antibiotics Zaps AIDS-Related Cancer Feb 2001 A chemically-modified common antibiotic appears to choke off the blood supply and then dramatically shrink disfiguring tumors associated with AIDS, researchers say. Among the first 18 patients with scores of purplish Kaposi's sarcoma tumors who took doses of chemically modified tetracycline, more than half had a clinical benefit. Eight of the patients achieved a partial response, meaning that half of their tumors shrank or disappeared. In one patient, all the evidence of the cancer vanished, and could not even be recognized after a biopsy, said Dr. Bruce Dezube, associate professor of medicine at Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass.
11/11/01 Switching off cancer Wednesday 29th December 1999 In the presence of the antibiotic tetracycline (given to mice in their drinking water), the oncogenic fusion gene is 'off' and the mice are healthy. When tetracycline is withdrawn (and thus the fusion gene switched on), the animals develop leukaemia and die within a few weeks. But by putting tetracycline back into the water -- and thus suppressing the fusion gene -- the researchers could achieve complete remission of the leukaemia. These results suggest that the initial oncogenic event (in this case, an overdose of BCR-ABL1) is necessary both to induce and, at least for some time thereafter, to maintain the cancer. Reversal of a single genetic event may therefore have therapeutic value, especially at early stages of the disease.
11/11/01 DG DISPATCH - AAAS: Chemically-Modified Tetracycline Shows Promise In Advanced Kaposi's Sarcoma SAN FRANCISCO, CA -- February 19, 2001 -- A chemically-modified form of tetracycline, Metastat(r), appears to have anti-angiogenesis properties and shows promise in treating Kaposi's sarcoma. According to researchers at the 2001 annual meeting of the American Association for the Advancement of Science here, the drug appears to have clinical impact even though the patients in the Phase I trial had advanced cancer. "We are very excited about this drug," said Dr. Bruce Dezube, associate professor of medicine at Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, who is testing Metastat, an investigational drug from CollaGenex Pharmaceuticals, Inc., Newtown, Pennsylvania. "We were also pleased that the drug appeared to work the way we expected it to and that there appeared to be few side effects."
11/11/01 A phase I and pharmacokinetic (PK) study of Col-3, an oral tetracycline analog and selective matrix metalloproteinase (MMP) inhibitor Col-3, a tetracycline analog, selectively inhibits expression and production of MMP-2 and -9, and reduces growth of primary and metastatic tumors at Css in the low micromolar range. This study evaluated the toxicologic and PK profiles of Col-3 on a protracted schedule in patients (pts) with solid malignancies
11/11/01 Inhibition of tumor cell invasiveness by chemically modified tetracyclines Curr Med Chem 2001 Feb;8(3):261-70 We demonstrate here that one of the chemically modified tetracyclines, 6-deoxy-6-demethyl-4-de(dimethylamino)tetracycline (CMT-3) can effectively inhibit ECM degradation mediated by COLO 205 cells or their conditioned medium We show here that CMT-3 displays multiple modes of action: inhibiting MMP activity, reducing levels of MMP expression, and exhibiting selective cytotoxicity towards some of the tumor cell lines
11/11/01 Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression Carcinogenesis 2000 Jun;21(6):1149-55 During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal anti-inflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis

Suramin
11/02/01 Old Drug Shows Promise For Helping Treat Advanced Lung Cancer Combining standard chemotherapy treatment with a drug once used to treat parasitic infections may give new hope to patients with lung cancer. Researchers at Ohio State University found that small doses of the drug suramin enhanced the effectiveness of standard chemotherapy drugs used to treat patients with advanced forms of lung cancer. The 12 patients in the study were treated with a combination of suramin and the chemotherapy drugs paclitaxel and carboplatin. After following the patients for an average of nine months, researchers found that the tumors had not progressed in eight of the patients. In fact, tumors had shrunk in seven of the patients.

Artesunate
10/19/01 The anti-malarial artesunate is also active against cancer. Int J Oncol 2001 Apr;18(4):767-73 Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines

Neutrexin
10/27/01 Oncolink clinical trials briefs Neutrexin
11/03/01 Neutrexin (TRIMETRAXATE)
11/03/01 Drug description Trimetrexate has been approved by the U.S. Food and Drug Administration for the treatment of moderate-to-severe PCP pneumonia in people with compromised immune systems
11/03/01 Hackensack Medical Center - Neutrexin Trial For patients with advanced (metastatic) disease: 1. Phase II trial of cryoablation for the treatment of unresectable colorectal hepatic metastasis 2. Phase III trial of leucovorin plus 5-FU plus/minus Neutrexin in previously untreated patients with advanced colorectal cancer

Celebrex/Lovastatin

Celebrex / Lovastatin References
6/4/2001 Biologically Useful Responses of Human Neoplasia to Celecoxib and Lovastatin. ASCO Abstracts, May 2001 Michael Snyderman, Mercy Hospital, Buffalo, NY
7/19/01 A Phase I-II Trial of Prolonged Administration of Lovastatin in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC) or of the Cervix.
11/11/01 Combined prenylation inhibitor therapy in drug-refractory cancers ASCO 1997 We selected Limonene (L), a monoterpene for combination with Lovastatin. L, a natural product, constitutes 20% v/v of citrus fruit peel oil and can be administered orally. In a pilot study we administered Lovastatin 40-80 mg/day plus L 2-4 ml/day po on monthly cycles to 6 patients Two of 6 patients revealed evidence of objective clinical response. A 50% decrease in a bi-dimensionally measurable pulmonary nodule in the head & neck patient and a >50% decline in CEA and CA15.3 level in the breast cancer patient, both of whom received no other therapy, were observed. Stable disease of 3 months duration in the prostate cancer patient, measured by PSA was also observed. Preliminary evidence of clinical response to this simple therapy is of interest and suggests that clinical trials focusing upon inhibitors of ras activation hold promise for therapy.

Cisplatin

Cisplatin References
9/15/01 Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma]. Gan To Kagaku Ryoho 2000 Jun;27(6):859-864 Kamata T, Morita A, Nakamoto A, Onishi I, Takeda T, Koyasaki N, Kanno M. Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months
9/15/01 Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy. J Gastroenterol 2000;35(11):864-869 Kaneki T, Koizumi T, Kawashima A, Tsushima K, Kubo K, Fujimoto K, Honda T, Akamatsu T. We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP).

Mitomycin

Mitomycin References
9/28/01 5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer Br J Cancer 2001 Apr 20;84(8):1023-8 Sobrero A, Guglielmi A, Cirillo M, Recaldin E, Frassineti GL, Aschele C, Ravaioli A, Testore P, Caroti C, Gallo L, Pessi MA, Cortesi E, Turci D, Grossi F, Labianca R. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity

Thalidomide

Thalidomide References

Herceptin

Herceptin References

New Drugs to Watch for in Future Clinical Trials
11/11/01 Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Clin Cancer Res 2001 Jul;7(7):2067-75 In the present study, we evaluated the relative potency and mechanism of action of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis. Cerivastatin is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines
11/11/01 Aspirin: The Next Generation Aspirin and other nonsteroidal anti-inflammatory agents exert their effects by blocking the action of enzymes that catalyze the conversion of arachidonic acid to prostaglandins. Aspirin irreversibly blocks two such enzymes, cyclooxygenases 1 and 2 (COX-1 and COX-2), by acetylation. Its analgesic and anti-inflammatory effects reflect inhibition of COX-2, whereas its antithrombotic effects--and potential for ulcerogenesis and renal impairment--reflect inhibition of COX-1. Aspirin's potency against COX-1 is 10 to 100 times greater than against COX-2. A selective COX-2 inhibitor would be a boon for rheumatic patients who take aspirin for extended periods. Evidence that long-term NSAID use reduces the incidence of colon cancer (and, mysteriously, also that of Alzheimer's disease), and the finding that colon cancer tissues contain high levels of COX-2 have spurred development of a new generation of COX-2 inhibitors. At least two are already well on their way to market, but their effects are reversible and short-lived. Researchers at Vanderbilt University have now synthesized a compound that acetylates COX-2 irreversibly. Known as APHS, this new drug is 60 times more reactive against COX-2 than aspirin, and 100 times more selective. Furthermore, it inhibits the growth of human cancer cells that express high levels of COX-2.
10/30/01 Clinical Trial A virus (SCH5800) that has been altered to carry a normal p53 gene-which may play a role in stopping or slowing down cancer development-will be infused through the hepatic artery as gene therapy for patients with colorectal cancer that has spread to the liver. To be eligible for this study, patients must not have received more than one prior chemotherapy regimen. Patients in this study will be randomized to receive gene therapy and the chemotherapeutic agent FUDR or FUDR alone. Study 3C-98-8, Heinz-Josef Lenz, M.D.
10/29/01 Radioactive microspheres treat liver cancer Friday, Oct 26 2001 Dr. Andrew Kennedy, assistant professor of radiation oncology at the University of Maryland Greenebaum Cancer Center, in Baltimore, and colleagues treated 19 patients with metastatic liver cancer (primarily secondary to colorectal cancer) with yttrium-90 insoluble glass microspheres (TheraSphere, MDS Nordion, Ottawa). As reported by Dr. Brian Carr, professor and chief of the liver cancer program, University of Pittsburgh Medical Center, Pennsylvania, and colleagues, treatment of primary hepatomas using the same radioactive microspheres appears to be both safe and well tolerated, even in patients whose livers are highly susceptible to radiation-induced damage.
10/31/01 Oncolytic Drugs dailydrugnews.com - promising compounds from ASCO
10/31/01 TLK-286
10/23/01 Second Zeltia drug shows cancer promise Tuesday, Oct 23 2001 A second marine-derived drug from Spanish biotechnology group Zeltia SA has shown promise in treating a range of human tumours, according to research published on Monday. The medicine, called Aplidine, was found to be effective in early Phase I studies involving 162 patients with thyroid, colorectal, kidney, neuroendocrine and skin cancers, Eric Raymond of the Institut Gustave Roussy, Villejuif, France, told the European Cancer Conference. Like Zeltia's most advanced anti-cancer drug, ET 743, Aplidine is derived from a sea quirt, a sponge-like creature that grows in clusters in the Mediterranean
10/23/01 Cancer gene therapy using survivin mutant adenovirus effective in animal model Tuesday, Oct 23 2001 Gene therapy using an engineered adenovirus that expresses a mutant form of survivin inhibits the growth of established tumors in mice, researchers from Yale University in New Haven, Connecticut report in the October issue of The Journal of Clinical Investigation. The lead author of both papers, Dr. Dario C. Altieri, noted in an interview with Reuters Health that the apoptosis inhibitor survivin "is abundant in a very high number of human cancers, but not in normal human tissues." Survivin is a negative prognostic factor that seems to mark more aggressive disease and unfavorable outcomes, he said.
10/23/01 Injectable cisplatin gel active in head and neck cancer Tuesday, Oct 23 2001 A cisplatin-containing gel that is injected directly into tumors of patients with advanced squamous cell carcinoma of the head and neck is associated with good response rates even when patients have received previous therapy. Dr. Jochen Werner, of Philipps University at Marburg Clinic, Marburg, Germany, and a multicentre team randomized 119 patients to receive a cisplatin-containing gel to which the vasoconstrictor epinephrine had been added (IntraDose Injectable Gel, Matrix Pharmaceutical). Another 59 patients were treated with a placebo gel.
10/19/01 Anti-K-ras ribozyme induces growth inhibition and increased chemosensitivity in human colon cancer cells. Cancer Gene Ther 2000 Mar;7(3):495-500
10/10/01 New class of drugs kills colon cancer cells A new class of drugs based on hydroxyurea, currently used for cancer and other indications, shows potent activity against colon cancer cells in vitro and in a mouse model, according to researchers from Europe. According to their report in the October 1st International Journal of Cancer, several of the compounds showed cancer-limiting activity in cells grown in the laboratory. In fact, the authors report, the drugs were unusually active against colon cancer cells that usually resist chemotherapy Int J Cancer 2001;94:89-96. (Abstract not available online at time of posting.)
10/9/01 Calreticulin-antigen DNA vaccine offers dual approach to cancer therapy Oct 4 2001 Combining antigen-specific immunotherapy and antiangiogenesis appears to be an effective method of fighting tumors, researchers report in the September issue of The Journal of Clinical Investigation. Dr. T.-C. Wu and colleagues at the Johns Hopkins Medical Institutions in Baltimore tested this approach in a murine tumor model using calreticulin (CRT), which has been shown to enhance antigen presentation and to have an antiangiogenic effect.
10/2/01 Novel molecule destroys tumor blood vessels in mice Tuesday, Oct 2 2001 An engineered molecule eradicates prostate cancer tumors in mice by binding with tissue factor on the surface of tumor blood vessels and activating an cytolytic immune attack, according to a report in the early online edition of the Proceedings of the National Academy of Sciences for October 9. This approach completely eradicated well-developed tumors, he said. The effect of treatment was seen within a day, and tumor size continued to decrease over the course of therapy. "When treatment was halted after about 2 months, the tumors had disappeared. About 4 months after therapy, the animals were dissected, and we could not find any evidence of any living tumor cells," Dr. Garen noted. The tumors affected are not only those injected with the vector, but also distant tumors, he added. "That's not surprising, because the icon molecule, once it gets into the blood, will seek out whatever tumors are expressing tissue factor on their blood vessels. With this one method you should be able to destroy any solid tumor." Blood vessels in healthy tissues are not harmed
9/10/01 PROLONGED SURVIVAL OF MUTIPLE LIVER METASATASES MODEL MICE BY INTRAVENOUS ADMINISTRATION OF REPLICABLE ADENOVIRUS WITH CEA PROMOTER CONTROLLED E1A AND 55K-DELETED E1B Tamotsu Sagawa, Minoru Takahashi, Tetsuya Sumiyoshi, Tsutomu Sato, Yasushi Sato, Satoshi Iyama, Junki Fukaura, Yasuyuki Yamada, Tetsuro Okamoto, Takatomi Oku, Yoshiro Niitsu 4th Department of Internal Medicine Sapporo Medical University School of Medicine, Japan
9/15/01 TITLE: Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression. AUTHOR: Zhou Q, Sherwin RP, Parrish C, Richters V, Groshen SG, Tsao-Wei D, Markland FS SOURCE: Breast Cancer Res Treat; 61(3):249-60 2000 UI: 20419185 We report the results of a multidisciplinary study on the inhibitory effect of a snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast cancer progression Contortrostatin is not cytotoxic to cancer cells, and does not inhibit proliferation of the breast cancer cells in vitro. However, contortrostatin inhibits angiogenesis induced by the breast cancer, as shown by immunohistochemical quantitation of the vascular endothelial cells in tumor tissue removed from the nude mice
5/15/01 Novel drug starves tumors lifelines Modified antibiotic shows promise, researchers say Feb 16, 2001 By Charlene Laino Metastat (tetracycline derivative) Dezube studied 18 HIV-infected patients with Kaposi's sarcoma
4/15/01 Telik's TLK286 is a small molecule drug candidate designed to target tumors that overexpress GST P1-1. Lexis-Nexus.com March 30, 2001 Phase II trials described
4/30/01 Drug data shows promise Andrew Clark Monday April 30, 2001 The Guardian (UK) Biotechnology company Antisoma is set to disclose encouraging data today on a breast cancer drug licensed from the Imperial Cancer Research Fund. The treatment, Therex, mimics the action of human antibodies in stimulating the body's defences against tumours. It revives the immune system in relapsed cancer patients, who often stop producing useful antibodies.
4/23/01 St John's wort used in cancer fight BBC News Monday, 23 April, 2001, 03:49 GMT 04:49 UK
4/23/01 March 27, 2001 Aeterna (AELA) Anticancer Drug Shows'Encouraging' Results in Early Trials -Neovastat, a drug derived from shark cartilage
4/23/01 AEterna's Lead Product, Neovastat, Significantly Increases Survival Time in Phase I/II Patients with Kidney Cancer-Neovastat/AE-941

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