Page 969 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 54 Cancer Chemotherapy 955

TABLE 54–2 Alkylating agents and platinum analogs: Clinical activity and toxicities.

Mechanism of
Alkylating Agent Action Clinical Applications Acute Toxicity Delayed Toxicity
Mechlorethamine Forms DNA cross- Hodgkin’s and non-Hodgkin’s Nausea and Moderate depression of peripheral
links, resulting in lymphoma vomiting blood count; excessive doses produce
inhibition of DNA severe bone marrow depression with
synthesis and leukopenia, thrombocytopenia, and
function bleeding; alopecia and hemorrhagic cys-
titis occasionally occur with cyclophos-
Chlorambucil Same as above CLL and non-Hodgkin’s Nausea and
lymphoma vomiting phamide; cystitis can be prevented with
adequate hydration; busulfan is associ-
Cyclophosphamide Same as above Breast cancer, ovarian cancer, Nausea and ated with skin pigmentation, pulmonary
non-Hodgkin’s lymphoma, vomiting fibrosis, and adrenal insufficiency
CLL, soft tissue sarcoma,
neuroblastoma, Wilms’ tumor,
rhabdomyosarcoma
Bendamustine Same as above CLL and non-Hodgkin’s Nausea and
lymphoma vomiting
Melphalan Same as above Multiple myeloma, breast Nausea and
cancer, ovarian cancer vomiting
Thiotepa Same as above Breast cancer, ovarian cancer, Nausea and
superficial bladder cancer vomiting
Busulfan Same as above CML Nausea and
vomiting
Carmustine Same as above Brain cancer, Hodgkin’s and Nausea and Myelosuppression; rarely interstitial lung
non-Hodgkin’s lymphoma vomiting disease and interstitial nephritis
Lomustine Same as above Brain cancer Nausea and
vomiting
Altretamine Same as above Ovarian cancer Nausea and Myelosuppression, peripheral neuropa-
vomiting thy, flu-like syndrome
Temozolomide Methylates DNA Brain cancer, melanoma Nausea and Myelosuppression, mild elevation in liver
and inhibits DNA vomiting, head- function tests, photosensitivity
synthesis and ache and fatigue
function
Procarbazine Methylates DNA Hodgkin’s and non-Hodgkin’s Central nervous Myelosuppression, hypersensitivity
and inhibits DNA lymphoma, brain tumors system depression reactions
synthesis and
function
Dacarbazine Methylates DNA Hodgkin’s lymphoma, Nausea and Myelosuppression, central nervous
and inhibits DNA melanoma, soft tissue sarcoma vomiting system toxicity with neuropathy, ataxia,
synthesis and lethargy, and confusion
function
Cisplatin Forms intrastrand Non-small cell and small cell Nausea and Nephrotoxicity, peripheral sen-
and interstrand lung cancer, breast cancer, vomiting sory neuropathy, ototoxicity, nerve
DNA cross-links; bladder cancer, cholangio- dysfunction
binding to nuclear carcinoma, gastroesophageal
and cytoplasmic cancer, head and neck cancer,
proteins ovarian cancer, germ cell
cancer
Carboplatin Same as cisplatin Non-small cell and small cell Nausea and Myelosuppression; rarely peripheral
lung cancer, breast cancer, vomiting neuropathy, renal toxicity, hepatic
bladder cancer, head and neck dysfunction
cancer, ovarian cancer
Oxaliplatin Same as cisplatin Colorectal cancer, Nausea and Myelosuppression, peripheral sensory
gastroesophageal cancer, vomiting, laryn- neuropathy, diarrhea
pancreatic cancer gopharyngeal
dysesthesias
CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia.