Page 980 - Basic _ Clinical Pharmacology ( PDFDrive )

966 SECTION VIII Chemotherapeutic Drugs

The incidence of pulmonary toxicity is increased in patients older MISCELLANEOUS ANTI-CANCER
than 70 years of age, in those who receive cumulative doses greater
than 400 units, in those with underlying pulmonary disease, and DRUGS
in those who have received prior mediastinal or chest irradiation. A large number of anti-cancer drugs that do not fit traditional
In rare cases, pulmonary toxicity can be fatal. Other toxicities are categories have been approved for clinical use; they are listed in
listed in Table 54–4. Table 54–5.

TABLE 54–5 Miscellaneous anti-cancer drugs: Clinical activity and toxicities.

Drug Mechanism of Action 1 Clinical Applications 1 Acute Toxicity Delayed Toxicity
Bortezomib Inhibitor of the 26S proteosome; Multiple myeloma, Nausea and Peripheral sensory neuropathy, diarrhea,
results in down-regulation of the mantle cell lymphoma vomiting, fever orthostatic hypotension, fever, pulmonary
NF-κB signaling pathway toxicity, reversible posterior leukoenceph-
alopathy (RPLS), congestive heart failure
(CHF), rare cases of QT prolongation
Carfilzomib Inhibitor of the 26S proteosome; Multiple myeloma Fever Fatigue, cardiac toxicity with CHF and
results in down-regulation of the myocardial infarction, myelosuppression,
NF-κB signaling pathway; maintains pulmonary toxicity, hepatotoxicity, ortho-
activity in bortezomib-resistant static hypotension
tumors
Erlotinib Inhibits EGFR tyrosine kinase leading Non-small cell lung can- Diarrhea Skin rash, diarrhea, anorexia, interstitial
to inhibition of EGFR signaling cer, pancreatic cancer lung disease
Imatinib Inhibits Bcr-Abl tyrosine kinase and CML, gastrointestinal Nausea and Fluid retention with ankle and periorbital
other receptor tyrosine kinases, stromal tumor (GIST), vomiting edema, diarrhea, myalgias, congestive
including PDGFR, and c-kit Philadelphia chromo- heart failure
some-positive ALL
Bosutinib Inhibits Bcr-Abl tyrosine kinase and CML Nausea and Diarrhea, fluid retention, myelosuppres-
retains activity in imatinib-resistant vomiting sion, skin rash hepatotoxicity
Bcr-Abl mutations except for the
T315I and V299L mutations. Inhibits
Src family tyrosine kinases.
Cetuximab Binds to EGFR and inhibits down- Colorectal cancer, head Infusion Skin rash, hypomagnesemia, fatigue,
stream EGFR signaling; enhances and neck cancer (used in reaction interstitial lung disease
response to chemotherapy and combination with radio-
radiotherapy therapy), non-small cell
lung cancer
Panitumumab Binds to EGFR and inhibits down- Colorectal cancer Infusion Skin rash, hypomagnesemia, fatigue,
stream EGFR signaling; enhances reaction interstitial lung disease
response to chemotherapy and (rarely)
radiotherapy
Bevacizumab Inhibits binding of VEGF-A to VEGFR Colorectal cancer, breast Hyperten- Arterial thromboembolic events, gastro-
leading to inhibition of VEGF signal- cancer, non-small cell sion, infusion intestinal perforations, wound healing
ing; inhibits tumor vascular perme- lung cancer, renal cell reaction complications, bleeding complications,
ability; enhances tumor blood flow cancer, glioblastoma proteinuria
and drug delivery multiformae
Ziv-aflibercept Inhibits binding of VEGF-A, VEGF-B, Colorectal cancer Hypertension Arterial thromboembolic events, gastro-
and PlGF to VEGFR leading to inhibi- intestinal perforations, wound healing
tion of VEGF signaling; inhibits tumor complications, bleeding complications,
vascular permeability; enhances diarrhea, mucositis, proteinuria
tumor blood flow and drug delivery
Sorafenib Inhibits multiple RTKs, including Renal cell cancer, hepa- Nausea, Skin rash, fatigue and asthenia, bleeding
raf kinase, VEGF-R2, VEGF-R3, and tocellular cancer hypertension complications, hypophosphatemia
PDGFR-β leading to inhibition
of angiogenesis, invasion, and
metastasis
Sunitinib, Inhibits multiple RTKs, includ- Renal cell cancer, GIST Hypertension Skin rash, fatigue and asthenia, bleeding
pazopanib ing VEGF-R1, VEGF-R2, VEGF-R3, complications, cardiac toxicity leading to
PDGFR-α and PDGFR-β leading to congestive heart failure in rare cases
inhibition of angiogenesis, invasion,
and metastasis
1
See text for acronyms.