Melphalan toxicity

MELPHALAN ANTIBIOTICS - NALIDIXIC ACID Risk of melphalan toxicity Uncertain Avoid co-administration... 

Owing to the favorable activity profile of 66, which acts as a prodrug of the active species 62, additional studies were conducted on 66 to establish its cell-based profile. It was determined that 66 potentiated chlorambucil (74) toxicity in cell lines expressing GST Pl-1, namely HT-29, HT4-1, SK OV-3, and SK VLB. Also, while 66 alone did not prevent tumor growth in the HT4-1 xenograph model, 66 increased by 56% the tumor growth inhibitory effect of melphalan (75). 

With chlorambucil and melphalan, although administered orally complaints of nausea and vomiting are minimal. The other toxic effects are comparable to those of cyclophosphamide. Chlorambucil has marked immunosuppressant activity. 

MELPHALAN CICLOSPORIN Risk of renal toxicity Additive effect Monitor U Es closely... 

Schallier D, Impens N, Warson F, Van Belle S, De Wasch G. Additive pulmonary toxicity with melphalan and busulfan therapy. Chest 1983 84(4) 492-3. 

Melphalan is active against multiple myeloma. It alsoi< active against brea.st. testicular, and ovarian carcinonn. The clinical toxicity is mainly hcmatologicul. which mum that the blotxl count must be followed carefully. Nausea ami vomiting are infrequent, but alopecia occurs. 

Chlorambucil, melphalan, and uracil mustard also have been associated with pulmonary fibrosis. Of the alkylating agents, only nitrogen mustard and thiotepa have not been reported to cause fibrotic pulmonary toxicity. ... 

Significant improvements were achieved with the drugs chlorambucil (Leukeran, 1952) and melphalan (Alkeran, 1954), both developed at the Chester Beatty Laboratory in London. These drugs were more water-soluble (and hence available by mouth rather than intravenous infusion) and more easily taken up by cancer cells. They were also less toxic to bone-marrow cells and have been widely used over the intervening years for the treatment of various leukaemias and other tumours. An interesting combination of the female sex hormone oestradiol with mechlorethamine was invented in Romania in 1966, and was marketed under the trade-name Estracyte (estra-mustine) for the treatment of prostatic cancer. 

The chnical toxicity of melphalan is mostly hematological and is similar to that of other alkylating agents. Nausea and vomiting are less frequent. Alopecia does not occur at standard doses, and changes in renal or hepatic function have not been observed. 

The alkylating agents differ in their patterns of antitumor activity and in the sites and severity of their side effects. Most cause dose-limiting toxicity to bone marrow and intestinal mucosa. Most alkylating agents, including nitrogen mustard, melphalan, chlorambucil, cyclophosphamide, and... 

ORAL ADMINISTRATION. A number of antineoplastic dni are administered orally. The oral route is convenient, economical, noninvasive, and often less toxic. Most oral dru are well absorbed when the gastrointestinal tract is functioning normally. Antineoplastic dru such as melphalan, busulfan, and chlorambucil are usually given orally. (Melphalan and busulfan are also available as injectable products for specific indications.) Most oral dru are administered by die patient in a home setting. The section on Educating die Fhtient and Family provide information to include in a teaching plan. 

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