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3 flg/mL are reached within 60 m; steady-state volume of distribution is 13 ! 6 Um2; cerebrospinal fluid to plasma concentration ratio is 29% ! m2; there is much less inrerpatient variability than with dacarbazine DRUG INTERACTIONS Temowlomide toxicity may be enhanced if given with other myelosuppressive drugs or therapies RESPONSE RATES SPECIAL PRECAUTIONS Myelosuppression is the major dose-limiting toxicity of temozolornide; monitoring for leukopenia and thrombocytopenia should continue throughout therapy; all cytotoxic drugs may be embryotoxic or teratogenic; investigational agents should not be used in pregnant or nursing patients TOXICITIES Hematologic: dose-limiting thrombocytopenia (and occasionally leukopenia) occur at approximately 1 glm2; patients who have been heavily pretreated with chemotherapy or radiotherapy have a greater risk of myelosuppression; GI: mild to moderate nausea and vomiting; Miscellaneous: rare alopecia, mild erythematous skin rash, renal toxicity, constipation, and headaches Response rates, both complete and partial, of 17% have been reported in the treatment of metastatic melanoma; varied responses have been reported in patients with high-grade astrocytomas and mycosis fungoides (patient numbers in most trials so far are small) PATIENT MONITORING CBC, including differential leukocyte count and platelet count, should be obtained during therapy to monitor for leukopenia and thrombocytopenia; health care professionals respon ible for monitoring patients on temowlomide therapy should be familiar with the less common adverse effects that can occur with therapy NURSING INTERVENTIONS Monitor treatment tolerance, weight, nutritional status; en ure that appropriate lab tests are conducted to monitor leukopenia and thrombocytopenia; ensure appropriate documentation and notify physician of all adverse effects and patient complaints in patients receiving investigational drugs; ensure that a consent form is signed by the patient ro receive investigational drugs; nausea and vomiting are mild to moderate; appropriate antiemetics should be given PATIENT INFORMATION Call the doctor immediately if intractable nau ea and vomiting occur or if vomiting occurs after taking the temozolomide capsules, unusual bruising and bleeding occurs, or temperature over lOl' F occurs; avoid exposure to people with infections FORMULATION Available as Temedal (Schering-Plough, Kenilworth, NJ) Hard gelatin capsules containing 20, 50, 100, and 250 mg are available for phase I and II trials; still investigational The information here is provided os guidan(e only.

25 ALKYLATING AGENTS LOMUSTINE Lomustine (also known a CeeNU and CCNU) is a nitrosourea derivative that ha demonstrated cytotoxic activity against a wide variation of malignancies. ng agents, lomustine is considered to be cell cycle nonspecific. Within 1 to 6 hours after oral administration oflomustine, peak metabolite concentrations occur. These metabolites are responsible for the alkylation and carbamoylation activity, which interfere with D A, RNA, and protein synthesis. Cross-resistance between lomustine and carmustine has occurred.

Ng agents, lomustine is considered to be cell cycle nonspecific. Within 1 to 6 hours after oral administration oflomustine, peak metabolite concentrations occur. These metabolites are responsible for the alkylation and carbamoylation activity, which interfere with D A, RNA, and protein synthesis. Cross-resistance between lomustine and carmustine has occurred. Lomustine and its metabolites are widely distributed in the body. Nitrosoureas as a class tend to be highly lipophilic, thus enhancing their ability to cross the blood-brain barrier and to be used in the treatment of meningeal leukemia and brain tumors.