Chemo-induced Toxicities Reviewed

Feb 2008 See paper from the UK on "'Side' Effects of Chemotherapeutic Agents" by Ng, Carr and Wigmore.

Chemotherapy-induced toxicities are common and serious clinical problems that adversely impact both the quality of life of cancer patients and the ability of patients to continue treatment for their cancer.

Very little has been accomplished to prevent or reduce chemotherapy-induced toxicities such as nerve damage (neurotoxicity), kidney damage (nephrotoxicity), and hearing impairment (ototoxicity).

There is a drug, Tavocept, that is aimed at preventing or reducing common and serious side effects, particularly nerve and kidney damage, associated with taxane and platinum drugs.

Taxanes are a family of drugs that have been shown to be effective in treating various types of cancer, including ovarian, breast, lung, and melanoma. Paclitaxel (frequently sold under the brand names TaxolŽ and OnxolŽ) is currently one of the largest revenue producing cancer drugs on the market with worldwide annual revenues of over $800 million in 2002. Paclitaxel is a widely used chemotherapeutic agent for cancers of the lung, breast, ovary, esophagus and other types of cancer and it has been a generic drug for the last three years. Paclitaxel is known as a taxane type of chemotherapy drug.

Docetaxel is another widely used taxane drug (sold under the name TaxotereŽ by Aventis) that is used in the treatment of cancers of the lung, breast, ovary and other common cancers. Despite the broad antitumor activity of taxanes, their clinical usefulness has been limited by common side effects such as painful nerve damage (neurotoxicity), reduction of white blood cell counts, liver damage, allergic reactions, nausea and vomiting, and other toxicities. For example, it is estimated that over 50% of patients receiving paclitaxel experience some form of drug-induced nerve damage.

Some taxane-induced side effects are so common, and in some instances so severe, that patients and their physicians may delay treatment, reduce the dose or discontinue therapy altogether. While medications designed to prevent or treat nausea, vomiting and decreased white blood cell counts are available, there are currently no treatments for other serious taxane-induced side effects, particularly nerve damage.

Platinum drugs, such as cisplatin and carboplatin, are used to treat patients with a number of common cancers. Current worldwide revenues of cisplatin and carboplatin are estimated to be more than $700 million annually. Both cisplatin and carboplatin can cause significant side effects, including nerve damage (neurotoxicity), nausea, vomiting, and bone marrow dysfunction.

Importantly, cisplatin can also cause kidney damage (nephrotoxicity). As is the case with taxanes, platinum drug-induced side effects often can result in treatment delays, reductions in dose or discontinuance of therapy altogether. Nerve damage has been reported for all doses and administration schedules of platinum drugs, but no effective therapies are available for the prevention or treatment of platinum drug-induced nerve damage.

Some treatments, including infusions of saline, are used to help prevent the development of kidney damage associated with cisplatin therapy. These treatments have been reported to produce side effects and commonly require additional monitoring during administration.

Source: This is the company that manufactures Tavocet, mentioned in the third paragraph.

Ann's NOTE: We believe in gathering information from many sources. It is usually possible to get very interesting information on other company's products from various company websites. They ARE 'competitors' of course.

Sent to us by Gregory Pawelski

PK Analysis of 5-FU Predicts Life-threatening Toxicities

Abstract #2052 ASCO, 2004

Warfarin (Coumadin ) & Some Chemotherapies CLASH

Clin Colorectal Ca, 9/05

Hiccups: Adverse Reaction to Chemo

JNCI, 5/15/02

Treatment for Intractable Hiccup:Methylphenidate
Adverse Drug Reactions Found Post FDA Approval
Accuracy of Clinician Reporting Chemo Adverse Effects
Unusual Complication: Herpes Simplex...

Clin Onc, 2/04

References for Correspondence
Hearing Problems with Cisplatin
Severe Nail Changes From Docetaxel

Eur J Dermatol, 11-12/03

Docetaxel-induced Nail Problems
Nail Changes From Docetaxel (Taxotere)
Suggestions for Nails/Nail Care
Frozen Glove to Reduce Docetaxel Skin Toxicity
Frozen Glove Reduced Skin/Nail Damage - Docetaxel
Risk Factors: Chemo-associated Venous Thromboembolism

Cancer, 12/05

Thromboembolism in Hospitalized Neutropenic Ca Pts
Thrombotic Complications
Hearing Loss: Cisplatin (Esp Every Two Weeks)

J Clin Onc, 2/06

Anthracyclines: Children's Arteries Damaged

J Clin Onc, 2/06

Serious Adverse Events GREATER Than Prior Reporting

JNCI, August, 2006

'Side' Effects of Chemotherapeutic Agents

Current Anaesthesia & Critical Care, March 2008 Article in Press, Uncorrected Proof

PERMANENT Hair Loss - Taxotere

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