MOA Route Clinical Applications Toxicity
affect nucleotide and nucleic acid synthesis, inhibit cell replication
ANTIMETABOLITES
by inhibiting enzyme
ANTIFOLATES
mucositis, diarrhea, myelosuppression w/
Methotrexate inhibit DHFR & TS; MTX polyglutamates inhibit FPGS IV, intrathecal, oral Breast, H&N, Osteogenic, etc (check book)
neutropenia & thrombocytopenia
mesothelioma, non-small cell lung CA (w/ myelosuppression, skin rash, mucositis, diarrhea,
Pemetrexed inhibit TS (S phase)
Cisplatin) fatigue (Vit B12, Folic acid --> reduce toxicity)
Pralatrexate inhibits DHFR & TS refractory T-cell lymphoma same as above
PURINE ANTAGONISTS
inhibits de novo purine ntd synthesis; incorporation of triphosphate myelosuppression, immunosuppression,
6-Mercaptopurine oral AML (childhood leukemia)
into RNA & DNA hepatotoxicity
6-Thioguanine same as above oral ALL (adult acute leukemia), AML same as above
inhibits DNA synthesis & repair, ribnucleotide reductase; myelosuppression, immunosuppression to CD4 &
Fludarabine incorporation of fludarabine triphosphat ito DNA; induction of parenteral low grade Non-Hodgkin's Lymphoma, CLL CD8 T cells --> px at risk for opportunistic infxns,
apoptosis; inhibit DNA polymerase a&b fever, myalgias, arthralgias
inhibits DNA synthesis & repair, ribnucleotide reductase;
hairy cell leukemia, CLL, low-grade non-
Cladribine incorporation of cladribine triphosphate ito DNA; induction of IV myelosuppression, immunosuppression
Hodgkin's lymphoma
apoptosis; inhibit DNA polymerase a&b
FLUOROPYRIMIDINES
FdUMP (DNA synthesis inhibition by binding w/ TS); FUTP myelosuppression, neurotoxicity, skin toxicity
5-Fluorouracil (interfere RNA processing & mRNA translation); FdUTP (inhibit IV colorectal CA, solid tumors (hand &foot syndrome), GI (nausea, vomiting,
DNA synthesis & function) mucositis, diarrhea)
hydrolyzed to 5-FU by thymidine phosphorylase directly into the metastatic breast CA, colorectal CA, diarrhea, hand foot syndrome, mucositis, nausea,
Capecitabine
tumor adjuvant tx of stage III colorectal CA vomiting, myelosuppression
DEOXYCYTIDINE
mucositis, nausea, vomiting, myelosuppression,
Cytarabine ara-CTP: inhibits DNA pol a&b, inhibits DNA chain elongation IV AML, NHL
neurotoxicity
pancreatic cancer, non small cell lung ca,
inhibits ribonucleotide reductase, incorporating gemcitabine
Gemcitabine bladder CA, ovarian CA, soft tissue neutropenia, nausea, vomiting, flu-like symptoms
triphosphate into DNA
sarcoma, NHL
PLANT ALKALOIDS
VINCA ALKALOIDS
inhibits tubulin polymerization leading to arrest in metaphase / BM suppression, neurotoxicity, alopecia,
Vinblastine HL, NHL, Breast and germ cell CA
inhibits mitosis mucositis, diarrhea, SIADH
ALL in children (+Prednisone), HL, NHL,
neurotoxicity w/ peripheral neuropathy, CN
Vincristine same as above MM, Ewing's sarcoma, neuroblastoma,
palsies, ataxia, seizures, SIADH
Wilm's tumor, rhabdomyosarcoma
breast CA, ovarian CA, non-small cell lung myelosuppression w/ neutropenia, constipation,
Vinorelbine same as above
CA SIADH, elevated liver fx, neurotoxicity
EPIPODOPHYLLOTOXIN
S
inhibits topoismerase II (DNA stand breakage) --> block cell germ cell CA, HL, NHL, small cell & non-
Etoposide IV alopecia, myelosuppression, hypotension
division in late S-G2 phase small cell CA, gastric CA
CAMPTOTHECINS
1st line: metastatic colorectal CA (+ 5-FU
converted to SN-38; potent inhibitor of topoisomerase I (cutting & and Leucovorin); 2nd line: metastatic
Irinotecan myelosuppression & diarrhea
religating DNA strands) colorectal CA (mono), gastroesophageal,
nonsmall cell, small cell lung CA
2nd line: advanced ovarian CA and small
Topotecan same
cell lung CA
TAXANES
ovarian, advanced breast, non small &
Myelosuppressionn, hypotension, arrythmias,
Paclitaxel mitotic spindle poison by high affinity binding to microtubules small cell lung CA, H&N, esophageal,
peripheral neuropathy; hypersensitivity
prostate, AIDS-related Kaposi's Sarcoma
advanced breast, non small & small cell
myelosuppression, hypersenstivity, fluid retention,
Docetaxel same as above lung CA, H&N, gastric, bladder, advanced
neurotoxicity
platinum-refractory ovaria CA
ANTITUMOR bind to DNA through intercalation between specific bases, cause
ANTIBIOTICS DNA strand scission
1) inhibition of topo 1; 2) bind to DNA thru intercalation; 3) bind to
myelosuppression, alopecia, red urine, mucositis,
Anthracyclines CM to alter fluidity and ion transport; 4) generate semiquinone free IV
cardiotoxicity; radiation recall reaction
radicals & oxygen free radicals
breast, endometrium, ovary, testicle,
thryoid, stomach, blader, liver, lung CA,
Doxorubicin soft tissue sarcoma, neuroblastoma,
Ewings sarcoma, osteosarcoma,
rhabdomyosarcoma
semisynthetic anthracycline glycoside; inhibit topo II, oxygen free
a) Idarubicin AML (+ Cytarabine)
radicals causing strand breaks; intercalates into DNA
early-stage node + breast, metastatic
b) Epirubicin analog
breast, gastroesphageal cancer
fever, red urine, cardiotoxicity, alopecia,
c) Daunorubicin same w/ idarubicin AML, ALL
myelosuppression
advanced, hormone refractory prostate blue discoloration of the fingernails, sclera, and
d) Mitoxantrone
cancer, low grade NHL, breast CA, AML urine
pediatric tumors: Wilm's , rhabdomyoSA,
intercalates into DNA between G-C; inhibits all forms of DNA
Dactinomycin germ cell tumor, gestational trophoblastic radiation recall reaction
dependent RNA synthesis (rRNA most sensitive)
disease
squamous cell CA of anus, SCCa of cervix,
acts as an alkylating agent and form cross-links w/ DNA; formation
Mitomycin breast, gastric, pancreatic; intravesical tx myelosuppression, mucositis, fatigue, HUS
of oxygen free radicals
for superficial bladder CA
HL, NHL, H&N, germ cell, SCCa of skin,
Bleomycin O2 free radicals bind to DNA causing strand breaks IV, IM, SubQ cervix, vulva; sclerosing agent for pulmonary toxicity
malignant pleural effusion
affect nucleotide and nucleic acid synthesis, inhibit cell replication
ANTIMETABOLITES
by inhibiting enzyme
ANTIFOLATES
mucositis, diarrhea, myelosuppression w/
Methotrexate inhibit DHFR & TS; MTX polyglutamates inhibit FPGS IV, intrathecal, oral Breast, H&N, Osteogenic, etc (check book)
neutropenia & thrombocytopenia
mesothelioma, non-small cell lung CA (w/ myelosuppression, skin rash, mucositis, diarrhea,
Pemetrexed inhibit TS (S phase)
Cisplatin) fatigue (Vit B12, Folic acid --> reduce toxicity)
Pralatrexate inhibits DHFR & TS refractory T-cell lymphoma same as above
PURINE ANTAGONISTS
inhibits de novo purine ntd synthesis; incorporation of triphosphate myelosuppression, immunosuppression,
6-Mercaptopurine oral AML (childhood leukemia)
into RNA & DNA hepatotoxicity
6-Thioguanine same as above oral ALL (adult acute leukemia), AML same as above
inhibits DNA synthesis & repair, ribnucleotide reductase; myelosuppression, immunosuppression to CD4 &
Fludarabine incorporation of fludarabine triphosphat ito DNA; induction of parenteral low grade Non-Hodgkin's Lymphoma, CLL CD8 T cells --> px at risk for opportunistic infxns,
apoptosis; inhibit DNA polymerase a&b fever, myalgias, arthralgias
inhibits DNA synthesis & repair, ribnucleotide reductase;
hairy cell leukemia, CLL, low-grade non-
Cladribine incorporation of cladribine triphosphate ito DNA; induction of IV myelosuppression, immunosuppression
Hodgkin's lymphoma
apoptosis; inhibit DNA polymerase a&b
FLUOROPYRIMIDINES
FdUMP (DNA synthesis inhibition by binding w/ TS); FUTP myelosuppression, neurotoxicity, skin toxicity
5-Fluorouracil (interfere RNA processing & mRNA translation); FdUTP (inhibit IV colorectal CA, solid tumors (hand &foot syndrome), GI (nausea, vomiting,
DNA synthesis & function) mucositis, diarrhea)
hydrolyzed to 5-FU by thymidine phosphorylase directly into the metastatic breast CA, colorectal CA, diarrhea, hand foot syndrome, mucositis, nausea,
Capecitabine
tumor adjuvant tx of stage III colorectal CA vomiting, myelosuppression
DEOXYCYTIDINE
mucositis, nausea, vomiting, myelosuppression,
Cytarabine ara-CTP: inhibits DNA pol a&b, inhibits DNA chain elongation IV AML, NHL
neurotoxicity
pancreatic cancer, non small cell lung ca,
inhibits ribonucleotide reductase, incorporating gemcitabine
Gemcitabine bladder CA, ovarian CA, soft tissue neutropenia, nausea, vomiting, flu-like symptoms
triphosphate into DNA
sarcoma, NHL
PLANT ALKALOIDS
VINCA ALKALOIDS
inhibits tubulin polymerization leading to arrest in metaphase / BM suppression, neurotoxicity, alopecia,
Vinblastine HL, NHL, Breast and germ cell CA
inhibits mitosis mucositis, diarrhea, SIADH
ALL in children (+Prednisone), HL, NHL,
neurotoxicity w/ peripheral neuropathy, CN
Vincristine same as above MM, Ewing's sarcoma, neuroblastoma,
palsies, ataxia, seizures, SIADH
Wilm's tumor, rhabdomyosarcoma
breast CA, ovarian CA, non-small cell lung myelosuppression w/ neutropenia, constipation,
Vinorelbine same as above
CA SIADH, elevated liver fx, neurotoxicity
EPIPODOPHYLLOTOXIN
S
inhibits topoismerase II (DNA stand breakage) --> block cell germ cell CA, HL, NHL, small cell & non-
Etoposide IV alopecia, myelosuppression, hypotension
division in late S-G2 phase small cell CA, gastric CA
CAMPTOTHECINS
1st line: metastatic colorectal CA (+ 5-FU
converted to SN-38; potent inhibitor of topoisomerase I (cutting & and Leucovorin); 2nd line: metastatic
Irinotecan myelosuppression & diarrhea
religating DNA strands) colorectal CA (mono), gastroesophageal,
nonsmall cell, small cell lung CA
2nd line: advanced ovarian CA and small
Topotecan same
cell lung CA
TAXANES
ovarian, advanced breast, non small &
Myelosuppressionn, hypotension, arrythmias,
Paclitaxel mitotic spindle poison by high affinity binding to microtubules small cell lung CA, H&N, esophageal,
peripheral neuropathy; hypersensitivity
prostate, AIDS-related Kaposi's Sarcoma
advanced breast, non small & small cell
myelosuppression, hypersenstivity, fluid retention,
Docetaxel same as above lung CA, H&N, gastric, bladder, advanced
neurotoxicity
platinum-refractory ovaria CA
ANTITUMOR bind to DNA through intercalation between specific bases, cause
ANTIBIOTICS DNA strand scission
1) inhibition of topo 1; 2) bind to DNA thru intercalation; 3) bind to
myelosuppression, alopecia, red urine, mucositis,
Anthracyclines CM to alter fluidity and ion transport; 4) generate semiquinone free IV
cardiotoxicity; radiation recall reaction
radicals & oxygen free radicals
breast, endometrium, ovary, testicle,
thryoid, stomach, blader, liver, lung CA,
Doxorubicin soft tissue sarcoma, neuroblastoma,
Ewings sarcoma, osteosarcoma,
rhabdomyosarcoma
semisynthetic anthracycline glycoside; inhibit topo II, oxygen free
a) Idarubicin AML (+ Cytarabine)
radicals causing strand breaks; intercalates into DNA
early-stage node + breast, metastatic
b) Epirubicin analog
breast, gastroesphageal cancer
fever, red urine, cardiotoxicity, alopecia,
c) Daunorubicin same w/ idarubicin AML, ALL
myelosuppression
advanced, hormone refractory prostate blue discoloration of the fingernails, sclera, and
d) Mitoxantrone
cancer, low grade NHL, breast CA, AML urine
pediatric tumors: Wilm's , rhabdomyoSA,
intercalates into DNA between G-C; inhibits all forms of DNA
Dactinomycin germ cell tumor, gestational trophoblastic radiation recall reaction
dependent RNA synthesis (rRNA most sensitive)
disease
squamous cell CA of anus, SCCa of cervix,
acts as an alkylating agent and form cross-links w/ DNA; formation
Mitomycin breast, gastric, pancreatic; intravesical tx myelosuppression, mucositis, fatigue, HUS
of oxygen free radicals
for superficial bladder CA
HL, NHL, H&N, germ cell, SCCa of skin,
Bleomycin O2 free radicals bind to DNA causing strand breaks IV, IM, SubQ cervix, vulva; sclerosing agent for pulmonary toxicity
malignant pleural effusion
