Page 976 - Basic _ Clinical Pharmacology ( PDFDrive )

962 SECTION VIII Chemotherapeutic Drugs

Vinblastine The main adverse effects are outlined in Table 54–4, and they
include nausea and vomiting, bone marrow suppression, and
Vinblastine is an alkaloid derived from the periwinkle plant alopecia. This agent is also a potent vesicant, and care must
Vinca rosea. Vinblastine and other vinca alkaloids are metabo-
lized by the liver P450 system, and the majority of the drug be taken in its administration. It has clinical activity in the
is excreted in feces via the hepatobiliary system. As such, dose treatment of Hodgkin’s and non-Hodgkin’s lymphomas, breast
modification is required in the setting of liver dysfunction. cancer, and germ cell cancer.

TABLE 54–4 Natural product cancer chemotherapy drugs: Clinical activity and toxicities.

Drug Mechanism of Action Clinical Applications Acute Toxicity Delayed Toxicity
Bleomycin Oxygen free radicals bind Hodgkin’s and non-Hodgkin’s Allergic reactions, Skin toxicity, pulmo-
to DNA causing single- and lymphoma, germ cell cancer, head fever, hypotension nary fibrosis, mucositis,
double-strand DNA breaks and neck cancer alopecia
Daunorubicin Oxygen free radicals bind AML, ALL Nausea and vomit- Cardiotoxicity (see
to DNA causing single- and ing, fever, red urine text), alopecia,
double-strand DNA breaks; (not hematuria) myelosuppression
inhibits topoisomerase II;
intercalates into DNA
Docetaxel Inhibits mitosis Breast cancer, non-small cell lung Hypersensitivity Neurotoxicity, fluid reten-
cancer, prostate cancer, gastric cancer, tion, myelosuppression
head and neck cancer, ovarian cancer, with neutropenia
bladder cancer
Doxorubicin Oxygen free radicals bind to Breast cancer, Hodgkin’s and non-Hodg- Nausea, red urine Cardiotoxicity (see text),
DNA causing single- and double- kin’s lymphoma, soft tissue sarcoma, (not hematuria) alopecia, myelosuppres-
strand DNA breaks; inhibits ovarian cancer, non-small cell and small sion, stomatitis
topoisomerase II; intercalates cell lung cancer, thyroid cancer, Wilms’
into DNA tumor, neuroblastoma
Etoposide Inhibits topoisomerase II Non-small cell and small cell lung can- Nausea, vomiting, Alopecia,
cer; non-Hodgkin’s lymphoma, gastric hypotension myelosuppression
cancer
Idarubicin Oxygen free radicals bind to AML, ALL, CML in blast crisis Nausea and Myelosuppression, muco-
DNA causing single- and double- vomiting sitis, cardiotoxicity
strand DNA breaks; inhibits
topoisomerase II; intercalates
into DNA
Irinotecan Inhibits topoisomerase I Colorectal cancer, gastroesophageal Diarrhea, nausea, Diarrhea, myelosuppres-
cancer, non-small cell and small cell vomiting sion, nausea and vomiting
lung cancer
Mitomycin Acts as an alkylating agent and Superficial bladder cancer, gastric can- Nausea and Myelosuppression,
forms cross-links with DNA; for- cer, breast cancer, non-small cell lung vomiting mucositis, anorexia and
mation of oxygen free radicals, cancer, head and neck cancer (in combi- fatigue, hemolytic-uremic
which target DNA nation with radiotherapy) syndrome
Paclitaxel Inhibits mitosis Breast cancer, non-small cell and small Nausea, vomit- Myelosuppression, periph-
cell lung cancer, ovarian cancer, gas- ing, hypotension, eral sensory neuropathy
troesophageal cancer, prostate cancer, arrhythmias,
bladder cancer, head and neck cancer hypersensitivity
Topotecan Inhibits topoisomerase I Small cell lung cancer, ovarian cancer Nausea and Myelosuppression
vomiting
Vinblastine Inhibits mitosis Hodgkin’s and non-Hodgkin’s lym- Nausea and Myelosuppression, muco-
phoma, germ cell cancer, breast cancer, vomiting sitis, alopecia, syndrome
Kaposi’s sarcoma of inappropriate secretion
of antidiuretic hormone
(SIADH), vascular events
Vincristine Inhibits mitosis ALL, Hodgkin’s and non-Hodgkin’s None Neurotoxicity with periph-
lymphoma, rhabdomyosarcoma, eral neuropathy, paralytic
neuroblastoma, Wilms’ tumor ileus, myelosuppression,
alopecia, SIADH
Vinorelbine Inhibits mitosis Non-small cell lung cancer, breast Nausea and Myelosuppression,
cancer, ovarian cancer vomiting constipation, SIADH
ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia.