Info

Agent

Clinical uses Mechanism of action

Common toxicities

Nitrogen mustard derivatives

Mechlorethamine HD, NHL Bifunctional alkylating agent with Acute two reactive groups5 ■ DLT0 = Myelosuppression (onset

■ Severe nausea/vomiting (onset 30 min to 2 h7)

■ Extravasation (vesicant) Chronic

■ Secondary malignancies

■ Secondary malignancies

Cyclo-phosphamide

NHL, HD, BMT, CLL, ANLL, ALL, myeloma

Activated by hepatic oxidase enzymes to reactive agent phosphoramide mustard

Acute

■ DLT = Myelosuppression (onset 7 days8)

■ Dose-dependent nausea/vomiting (onset 8 h)

■ Hemorrhagic cystitis (onset ranges from 24 h to several weeks9)

■ Nephrotoxicity Chronic

■ Nephrotoxicity

Melphalan

Myeloma, BMT

l-phenylalanine mustard; classic bifunctional alkylating agent

Acute

■ DLT = Myelosuppression: prolonged and cumulative (onset 7 days, nadir up to 4-6 weeks after therapy10)

■ Dose-dependent nausea/ vomiting/mucositis

Chronic

■ Secondary malignancies, including AML and myelodysplasia

Chlorambucil

CLL, NHL, HD

Aromatic analog of nitrogen mustard; bifunctional alkylating agent with selective cytotoxicity for lymphocytes

Acute

■ DLT = Myelosuppression (onset 7 days, recovery 28 days11)

Chronic

■ Secondary malignancies, including acute leukemias

Alkyl sulfonates Busulfan

BMT, CML

Bifunctional alkylating agent with greater cytotoxicity to myeloid cell lines

Acute

■ DLT = Myelosuppression (onset 7-10 days12)

■ Mild nausea/vomiting

■ Hepatic VOD (with

■ Skin hyperpigmentation

■ Generalized tonic-clonic seizures doses > 16 mg/day12)

■ Skin hyperpigmentation

■ Generalized tonic-clonic seizures

Chronic

■ Interstitial pulmonary fibrosis (may occur 1-10 years after therapy12,13)

■ Secondary malignancies

Table 101.1

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