Table 1.
Molecular targeted therapy agents (all oral except as indicated)
| Class/drug | Target (s)/indication (s) | Common adverse effects/warnings |
|---|---|---|
| ALK inhibitor | Class effects: CYP3A4 drug interactions; GI symptoms; embryo-fetal toxicity; bradycardia; ILD; hepatotoxicity; QTc interval prolongation | |
| Alectinib (Alecensa®)[22] | RTK ALK, RET and downstream, STAT3 and AKT; ALK-positive metastatic NSCLC that has progressed or patient is intolerant of crizotinib | Fatigue, constipation, edema, myalgia Warnings: Hepatotoxicity, ILD, bradycardia, severe myalgia and creatine phosphokinase elevation, embryo-fetal toxicity |
| Brigatinib (Alunbrig®)[23] | RTK ALK, ROS1, IGF-1R, FLT-3, as well as EGFR deletion and point mutations. Also EMLA4-ALK and NPM-ALK fusion proteins | Nausea, diarrhea, fatigue, cough, headache Warnings: ILD, HTN, bradycardia, visual disturbances, CPK elevations, pancreatic enzyme elevation, hyperglycemia, embryo-fetal toxicity |
| Ceritinib (Zykadia®)[24] | RTK ALK, IGF-1R, InsR, ROS1; ALK+ metastatic NSCLC | Diarrhea, nausea, fatigue, vomiting, abdominal pain, decreased appetite, and weight loss Warnings: Severe/persistent GI toxicity, hepatotoxicity, ILD, QT interval prolongation, hyperglycemia, bradycardia, pancreatitis, embryo-fetal toxicity |
| Crizotinib (Xalkori®)[25] | RTK ALK, ROS-1; ALK+or ROS-1 positive metastatic NSCLC | Vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy Warnings: Hepatotoxicity, ILD, QT interval prolongation, bradycardia, severe visual loss, embryo-fetal toxicity |
| Angiogenesis inhibitors | Class effects: HTN, proteinuria, bleeding/hemorrhage, GI perforation/fistula, thrombotic events, impaired wound healing; embryo-fetal toxicity | |
| Axitinib (Inlyta®)[26] | VEGF receptors on endothelial cells lining blood vessels; advanced RCC | Diarrhea, HTN, fatigue, decreased appetite, nausea, dysphonia, PPES (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation Warnings: HTN, arterial and venous thrombotic events, hemorrhage, cardiac failure, GI perforation/fistula, hypothyroidism, RPLS, proteinuria, elevated LFTs, embryo-fetal toxicity |
| Cabozantinib (Cabometyx™)[27] | VEGF 1, 2, 3; MET, RET, ROS1, others. Advanced RCC | Diarrhea, fatigue, nausea, decreased appetite, PPES, HTN, vomiting, decreased weight, constipation Warnings: Hemorrhage, GI perforation/fistula, HTN and hypertensive crisis, severe diarrhea, palmar-plantar erythrodysesthesia (hand-foot) syndrome, RPLS, embryo-fetal toxicity |
| Cabozantinib (Cometriq™)[28] | MET, HGF; VEGFR 1, 2, 3; RET, KIT, FLT-3, others. Progressive, metastatic medullary thyroid cancer | Diarrhea, stomatitis, PPES, decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, HTN, abdominal pain, constipation, elevated LFTs, increased alkaline phosphatase, neutropenia, thrombocytopenia, hypocalcemia, hypophosphatemia Warnings: Thrombotic events, wound complications, HTN, osteonecrosis of the jaw, PPES, proteinuria, RPLS, embryo-fetal toxicity |
| Levatinib (Lenvima®)[29] | VEGFR1, 2, 3; Locally recurrent or metastatic progressive, RAI-refractory differentiated thyroid cancer; RCC | HTN, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, PPES, abdominal pain, and dysphonia Warnings: HTN (control before treatment), cardiac failure, arterial thrombotic events, hepatotoxicity, proteinuria, severe diarrhea, renal failure, GI perforation/fistula, QT-interval prolongation, hypocalcemia, RPLS, hemorrhage, thyroid dysfunction, embryo-fetal toxicity |
| Pazopanib (Votrient®)[30] | VEGFR 1, 2, 3; PDGF-R, FGFR; Advanced RCC; advanced soft tissue sarcoma | Diarrhea, HTN, hair color changes (depigmentation), nausea, anorexia, vomiting Warnings: Hepatotoxicity, prolonged QT intervals and torsades de pointes, cardiac dysfunction, hemorrhage, thrombotic events, thrombotic micro-angiopathy, GI perforation/fistula, ILD, RPLS, HTN, hypothyroidism, proteinuria, infection, embryo-fetal toxicity |
| Regorafenib (Stivarga™)[31] | VEGFR 2, 3; PDGF-R, RET, KIT, RAF; metastatic CRC; locally advanced unresectable or metastatic GIST, hepatocellular carcinoma previously treated with sorafenib | Pain, HFSR, asthenia/fatigue, diarrhea, decreased appetite/food intake, HTN, infection, dysphonia, fever, mucositis, hyperbilirubinemia, weight loss, rash, nausea Warnings: Hepatotoxicity, infections, hemorrhage, GI perforation or fistula, dermatologic toxicity, HTN, cardiac ischemia/MI, RPLS, sound healing complications, embryo-fetal toxicity |
| Sorafenib (Nexavar®)[32] | VEGFR2, PDGF, RAF; unresectable hepatocellular cancer; advanced RCC; locally recurrent or metastatic, progressive differentiated thyroid carcinoma refractory to RAI | Diarrhea, fatigue, infection, alopecia, HFSR, rash, weight loss, decreased appetite, nausea, GI and abdominal pain, HTN, hemorrhage Warnings: Cardiac ischemia/MI, bleeding, HTN, dermatologic toxicities, GI perforation, QT prolongation, drug-induced hepatitis, embryo-fetal toxicity, impairment of TSH suppression |
| Sunitinib (Sutent®)[33] | PDGF-R, VEGFR 1, 2, 3; KIT, FLT-3, RET; GIST after disease progression or intolerance to imatinib mesylate; advanced RCC; progressive, well-differentiated pNET | Fatigue, asthenia, fever, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain, constipation, HTN, peripheral edema, rash, HFSR, skin discoloration, dry skin, hair color changes, altered taste, headache, backpain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding Warnings: Hepatotoxicity, embryo-fetal toxicity, cardiovascular events, prolonged QT intervals and Tirsades de Pointes, HTN, hemorrhagic events, TLS, thrombotic microangiopathy, proteinuria, dermatologic toxicities, thyroid dysfunction, hypoglycemia, osteonecrosis of the jaw, impaired wound healing, adrenal hemorrhage |
| Vandetanib (Caprelsa®)[34] | VEGFR 2, EGFR 1; symptomatic or progressive medullary thyroid cancer in patients with metastatic or locally advanced unresectable disease | Diarrhea/colitis, rash, aneiform dermatitis, nausea, headache, HTN, URI, decreased appetite, abdominal pain Warnings: Prolonged QT, torsades de pointes, and sudden death; severe dermatologic toxicities; ILD; ischemic cerebrovascular events, hemorrhage, heart failure, diarrhea, HTN, RPLS; embryo-fetal toxicity |
| Ziv-aflibercept (Zaltrap®)[35] (Inravenous) | VEGF (recombinant fusion protein that is a decoy [VEGF trap]); metastatic CRC in combination with FOLFIRI | Leukopenia, diarrhea, neutropenia, proteinuria, increased ALT and AST, HTN, weight loss, stomatitis, fatigue, thrombocytopenia, decreased appetite, epistaxis, abdominal pain, dysphonia, increased serum creatinine, headache Warnings: Fistula formation, HTN, arterial thromboembolic events, proteinuria, neutropenia and neutropenic complications, diarrhea and dehydration, RPLS, hemorrhage, GI perforation, compromised wound healing |
| Bcl-2 inhibitor (restores apoptosis) | Class effects: TLS; embryo-fetal toxicity; neutropenia, drug interactions | |
| Venetoclax (Venclexta®)[17] | Bcl-2; CLL with 17p deletion mutation | Neutropenia, diarrhea, nausea, anemia, URI, thrombocytopenia, fatigue Warnings: TLS, neutropenia, embryo-fetal toxicity, live immunizations contraindicated |
| BCR-ABL kinase inhibitors | Class effects: CYP3A4 drug interactions, edema, bone marrow suppression; embryo-fetal toxicity | |
| Bosutinib (Bosulif®)[36] | BCR-ABL kinase, most resistant forms; adults with Ph + CML with relapsed disease | Diarrhea, nausea, thrombocytopenia, rash, vomiting, abdominal pain, respiratory tract infections, anemia, pyrexia, LFT abnormalities, fatigue, cough, headache Warnings: GI toxicity, myelosuppression, hepatotoxicity, fluid retention, renal toxicity, embryo-fetal toxicity |
| Dasatinib (Sprycel®)[37] | BCR-ABL kinase, other kinases including SRC; newly diagnosed PH + CML in chronic phase; chronic accelerated or myeloid or lymphoid blast phase PH + CML; resistant PH + ALL; pediatric PH + CML in chronic phase | Myelosuppression, fluid retention events, diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue, nausea, musculoskeletal pain Warnings: Myelosuppression and bleeding events, fluid retention, cardiac dysfunction, pulmonary arterial HTN, QT prolongation, severe dermatologic reactions, TLS, embryo-fetal toxicity, adverse effect on growth and development in pediatric patients |
| Imatinib mesylate (Gleevec®)[38] | BCR-ABL kinase; newly diagnosed Ph+ CML in chronic phase (adult, children); Ph+ CML in blast crisis/accelerated phase/chronic phase; relapsed refractory Ph+ ADD (adults); newly diagnosed Ph+ ALL children; certain MDS in adults | Edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue, abdominal pain Warnings: Edema and severe fluid retention, cytopenias, severe CHF and left ventricular dysfunction, severe hepatotoxicity, severe hemorrhage, GI perforation, cardiogenic shock, bullous dermatologic reactions, hypothyroidism, embryo-fetal toxicity, growth retardation in children, TLS, renal toxicity, changes in mental status |
| Nilotinib (Tasigna®)[39] | BCR-ABL kinase; newly diagnosed Ph+ CML in chronic phase (adult); Ph+ CML in chronic/accelerated phases (adult) | Nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, night sweats, myelosuppression Warnings: Myelosuppression, cardiac and arterial vascular occlusive events, pancreatitis, hepatotoxicity, electrolyte abnormalities, TLS, hemorrhage, drug interactions, caution in patients with total gastrectomy, embryo-fetal toxicity, fluid retention (effusions) |
| Ponatinib (Iclusig®)[40] | BCR-ABL kinase; CML in chronic/accelerated/blast phase or Ph+ for whom no other TKI inhibitor is indicated; adults with T3151-positive CML or Ph+ ALL | Abdominal pain, rash, constipation, headache, dry skin, fatigue, HTN, pyrexia, arthralgia, nausea, diarrhea, increased serum lipase, vomiting, myalgia, extremity pain Warnings |
| BRAF and MEK inhibitors | Class effects: New primary malignancies, hemorrhage, HTN, eye problems, GI symptoms, CYP3A4 drug interactions, embryo-fetal toxicity | |
| Cobimetinib (Cotellic®)[41] MEK inhibitor | Mutated BRAF, reversible inhibitor of MAPK/extracellular signal regulated kinase 1 (MEK1, MEK2); unresectable or metastatic melanoma with BRAF V600E or V600K mutation in combination with vemurafenib | Diarrhea, photosensitivity reaction, nausea, pyrexia, vomiting, increased LFTs, increased CPK, hypophosphatemia, hyponatremia, lymphopenia Warnings: New primary malignancies, hemorrhage, cardiomyopathy, severe dermatologic reaction, serous retinopathy and retinal vein occlusion, hepatotoxicity, rhabdomyolysis, embryo-fetal toxicity |
| Dabrafenib (Tafinlar®)[42] BRAF inhibitor | Mutated BRAF; unresectable or metastatic melanoma with BRAF V600E mutation; metastatic NSCLC with BRAF V600E mutation | Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, PPES, decreased appetite, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, hemorrhage Warnings: New primary malignancies, tumor promotion in BRAF wild-type tumors, hemorrhage, cardiomyopathy, uveitis, serious febrile reactions, serious skin toxicity, hyperglycemia, risk of hemolytic anemia in patients with G-6-PD, embryo-fetal toxicity |
| Trametinib (Mekinist®)[43] MEK inhibitor | MEK pathway; unresectable metastatic melanoma with BRAF V600E or V600K mutation, in combination with dabrafenib; metastatic NSCLC with BRAF V600E mutation. | Rash, diarrhea, lymphedema, pyrexia, nausea, rash, chills, diarrhea, vomiting, HTN, peripheral edema, dry skin, decreased appetite, hemorrhage Warnings: New primary malignancies, hemorrhage, colitis and GI perforation, venous thromboembolism, cardiomyopathy, ocular toxicities, ILD, serious febrile reactions, serious skin toxicities, hyperglycemia, embryo-fetal toxicity |
| Vemurafenib (Zelboraf®)[44] BRAF inhibitor | Mutated BRAF; malignant melanoma with BRAF V600E mutation; erdheim-Chester disease with BRAF V600 mutation | Arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, skin papilloma, prolonged QT-interval Warnings: New primary cutaneous malignancy, new noncutaneous squamous cell carcinoma, other malignancies, tumor promotion in BRAF wild-type melanoma, serious hyper-sensitivity reactions including anaphylaxis, severe dermatologic reactions, QT-prolongation, hepatotoxicity, photosensitivity, serious ophthalmologic reactions, embryo-fetal toxicity, radiation sensitization/recall, renal failure, Dupuytren's contracture and plantar fascial fibromatosis |
| BTK inhibitor | Class effects: cytopenias (infection and hemorrhage); HTN; 2nd primary malignancies; TLS; embryo-fetal toxicity | |
| Acalabrutinib (Calquence®)[45] | Bruton's tyrosine kinase (signaling molecule of the B-cell antigen receptor); Mantle cell lymphoma | Anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, bruising Warnings: Hemorrhage, infections, cytopenias, second primary malignancies, atrial fibrillation, and flutter |
| Ibrutinib (Imbruvica®)[46] | Bruton's tyrosine kinase (signaling molecule of the B-cell antigen receptor); MCL, CLL/SLL, CLL/SLL with 17p deletion mutation; WM, MZL, cGVHD | Neutropenia, thrombocytopenia, diarrhea, anemia, musculoskeletal pain, rash, nausea, bruising, fatigue, hemorrhage, pyrexia, muscle spasms Warnings: Hemorrhage, cytopenias, atrial fibrillation, HTN, second primary malignancies, TLS, embryo-fetal toxicity |
| Cyclin-dependent kinase inhibitor | Class effects: Neutropenia; embryo-fetal toxicity; CYP3A4 drug interactions; GI symptoms | |
| Abemaciclib (Verzenio™)[14] | CDKs 4, 6 (which allow cells to progress through G1 and S phases of cell cycle); together with fulvestrant, or as a single agent in | Diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, thrombocytopenia Warnings: Diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, embryo-fetal toxicity |
| women with HR+, HER-2-negative advanced or metastatic breast who have progressed on endocrine therapy or endocrine/chemotherapy (when given as monotherapy) | ||
| Palbociclib (Ibrance®)[47] | CDKs 4, 6 (which allow cells to progress through G1 and S phases of cell cycle); postmenopausal women with ER+, HER2- advanced BC, with letrozole or fulvestrant. | Neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anemia, alopecia, diarrhea, thrombocytopenia, rash, vomiting, decreased appetite, asthenia, pyrexia Warnings: Neutropenia, embryo-fetal toxicity |
| Ribociclib (Kisqali) [48] | Cyclin Dependent Kinase (CDK) s 4, 6 (which allow cells to progress through G1 and S phases of cell cycle); postmenopausal women with ER+, HER2- advanced or metastatic BC, with an aromatase inhibitor | Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain Warnings: QT-interval prolongation on ECG, neutropenia, embryo-fetal toxicity |
| Epidermal growth factor TKIs, small molecule | Class toxicity: skin rash, diarrhea, ILD, embryo-fetal toxicity, CYP3A4 and/or P-gp drug interactions | |
| Afatinib (Gilotrif®)[49] | EGFR with exon 19 deletions or exon 21 (L858R) substitution Metastatic NSCLC including EGFR with exon 19 deletions or exon 21 (L858R) substitution mutations | Diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus Warnings: Diarrhea, bullous and exfoliative skin disorders, ILD, hepatotoxicity, keratitis, embryo-fetal toxicity |
| Erlotinib (Tarceva®)[50] | EGFR with exon 19 deletions or exon 21 (L858R) substitution EGFR1-positive locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations; EGFR1 positive locally advanced or metastatic pancreatic cancer, together with gemcitabine | Rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, vomiting Warnings: ILD, renal failure, hepatotoxicity, GI perforation, bullous and exfoliative skin disorders, CVA, microangiopathic hemolytic anemia, ocular disorders, hemorrhage in patients taking warfarin, embryo-fetal toxicity |
| Gefitinib (Iressa®)[51] | EGFR with exon 19 deletions or exon 21 (L858R) substitution Metastatic NSCLC having EGFR exon 19 deletions or exon 21 (L858R) substitution mutations | Skin reactions, diarrhea Warnings: ILD, hepatotoxicity, GI perforation, diarrhea, ocular disorders, bullous and exfoliative skin disorders, embryo-fetal toxicity |
| Lapatinib (Tykerb®)[52] | EGFR1, EGFR2 (HER-2); advanced or metastatic HER2+breast cancer with capecitabine, or with letrozole | With Capecitabine, diarrhea, PPES, nausea, rash, vomiting, fatigue; when given with letrozole, diarrhea, rash, nausea, fatigue Warnings: Decreased LVEF, hepatotoxicity, diarrhea, ILD, prolonged QT interval, severe cutaneous reactions, embryo-fetal toxicity |
| Neratinib (Nerlynx®)[53] | HER-2 Extended adjuvant therapy of early stage HER-2 overexpressed/amplified breast cancer to follow adjuvant trastuzumab-based adjuvant therapy | Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, increased AST or ALT, nail disorder, dry skin, abdominal distention, decreased weight, UTI Warnings: Diarrhea, hepatotoxicity, embryo-fetal toxicity |
| Osimertinib (Tagrisso®)[54] | EGFR1 with T790M mutation Metastatic NSCLC having EGFR T790M mutation | Diarrhea, rash, dry skin, nail toxicity, fatigue Warnings: ILD, QTc interval prolongation, cardiomyopathy, keratitis, embryo-fetal toxicity |
| FLT3 kinase inhibitor | Class effects: Nausea, vomiting, diarrhea, embryo-fetal toxicity | |
| Midostaurin (Rydapt®)[55] | FLT3, KIT, PDGFRα/β, VEGFR2, members of the serine/threonine kinase PKC family; newly diagnosed FLT3 mutation positive AML together with standard chemotherapy; aggressive systemic mastocytosis; systemic mastocytosis with hematologic neoplasm; mast cell leukemia | Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, URI, diarrhea, edema, abdominal pain, fatigue, constipation, pyrexia, headache, dyspnea Warnings: Pulmonary toxicity, embryo-fetal toxicity |
| Hedgehog pathway inhibitors | Class effects: Embryo-fetal toxicity (negative pregnancy test before starting drug, effective contraception, no donation of blood, sperm); muscle spasms; risk of increased CK; GI symptoms | |
| Sonidegib (Odomzo®)[56] | SMO, a transmembrane signal transduction protein; adults with locally advanced basal cell carcinoma, recurrent after surgery, RT or in unresectable patients | Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased appetite and weight, myalgia, abdominal pain headache, pain, vomiting, pruritus Warnings: Musculoskeletal adverse reactions with increased serum CK |
| Vismodegib (Erivedge®)[57] | SMO, a transmembrane signal transduction protein; locally advanced or metastatic basal cell carcinoma | Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, ageusia. Warnings: Teach patient not to donate blood during or for 24 months after drug; teach male patient not to donate semen during or for 3 months after therapy; premature fusion of epiphyses |
| HDAC inhibitors | Class effects: Cytopenias (infection and bleeding); hepatotoxicity; TLS; embryo-fetal toxicity; GI symptoms; drug interactions | |
| Belinostat (Beleodaq®) (IV)[58] | HDAC (enzyme that prevents uncoiling of DNA strand so genes can be transcribed), so inhibition leads to cell-cycle arrest and apoptosis; Relapsed or refractory peripheral T-cell lymphoma | Nausea, fatigue, pyrexia, anemia, vomiting Warnings: Thrombocytopenia, infection, hepatotoxicity, TLS, embryo-fetal toxicity |
| Panobinostat (Farydak®)[59] | HDAC; multiple myeloma, in combination with bortezomib and dexamethasone | Diarrhea, afatigue, nausea, peripheral edema, decreased appetite, pyrexia, vomiting Warnings: Hemorrhage, hepatotoxicity, embryo-fetal toxicity |
| Romidepsin (Isodax®)[60] (IV) | HDAC; CTCL; PTCL | Neutropenia, lymphopenia, thrombocytopenia, infections, nausea, fatigue, vomiting, anorexia, anemia, ECG T-wave changes Warnings: Myelosuppression, infections, ECG changes, TLS, embryo-fetal toxicity |
| Vorinostat (Zolinza®)[61] | HDAC; CTCL | Diarrhea, fatigue, nausea, thrombocytopenia (may be severe with GI bleeding if combined with another HDAC inhibitor), anorexia, dysgeusia Warnings: PE and DVT; thrombocytopenia and anemia; GI toxicity; hyperglycemia; clinical chemistry abnormalities; embryo-fetal toxicity |
| IDH2 inhibitor | Class effects: embryo-fetal toxicity, possible differentiation syndrome | |
| Enasidenib (Idhifa®)[62] | Mutated IDH2; AML, refractory or relapsed, with IDH2 mutation | Nausea, vomiting, diarrhea, elevated BR, decreased appetite Warnings: Embryo-fetal toxicity |
| mTOR inhibitor | Class effects: CYP3A4 drug interactions; pneumonitis; embryo-fetal toxicity; GI symptoms; impaired wound healing; renal failure; hyperglycemia | |
| Everolimus (Afinitor®)[63] | mTOR; postmenopausal advanced ER+HER2-breast cancer; advanced RCC; progressive unresectable PNET (adults); renal angiomyolipoma (adults) | Stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, asthenia, fever, cough, headache, decreased appetite, respiratory tract infection. Warnings: Noninfectious pneumonia, infections, angioedema, stomatitis, renal failure, impaired wound healing, laboratory test alterations, embryo-fetal toxicity, avoid live vaccinations and close contact with those who have received live vaccines |
| Temsirolimus (Torisel®) (IV) [64] | mTOR; advanced RCC | Rash, asthenia, mucositis, nausea, edema, anorexia, laboratory abnormalities Warnings: HSRs/infusion reactions; hepatic impairment, hyperglycemia and hyperlipidemia; infections, ILD, bowel perforation; renal failure; abnormal wound healing; embryo-fetal toxicity; elderly may have more diarrhea, edema, and pneumonia; avoid live vaccinations and close contact with those who have received live vaccines |
| PARP inhibitors | Class effects: MDS/AML transformation, embryo-fetal toxicity | |
| Olaparib (Lynparza®)[65] | PARP-1, 2, 3; germline BRCA mutated recurrent or advanced ovarian cancer (actual or suspected) | Anemia, nausea, fatigue, vomiting, nasopharyngitis, URI/influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, stomatitis, laboratory abnormalities, CYP3A4 drug interactions Warnings: MDS/AML, pneumonitis, embryo-fetal toxicity |
| Niraparib (Zejula®)[66] | Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a CR or PR after platinum-based chemotherapy | Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal l pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, UTI, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, HTN Warnings: MDS/AML, bone marrow suppression, cardiovascular effects, embryo-fetal toxicity |
| Rucaparib (Rubraca™)[67] | PARP-1, 2, 3; germline and/or somatic BRCA mutated advanced ovarian cancer, after 2 or more prior chemotherapies | Nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, dyspnea, laboratory abnormalities Warnings: MDS/AML, embryo-fetal toxicity |
| PI3K inhibitor | Class effects: Neutropenia; severe cutaneous reactions; embryo-fetal toxicity | |
| Copanlisib (Aliqopa™)[68] [IV administration] | PI3K sends signals to B lymphocytes telling them where to find and attach to lymph nodes and bone marrow stroma. Drug inhibits PI3K; Relapsed follicular lymphoma after 2 prior therapies | Hyperglycemia, diarrhea, decreased general strength and energy, HTN, leukopenia, neutropenia, nausea, lower respiratory infection, thrombocytopenia Warnings/precautions: Severe infections, noninfectious pneumonitis, severe cutaneous toxicity, embryo-fetal toxicity; control hyperglycemia and HTN before treatment |
| Idelalisib (Zydelig®)[69] | PI3K sends signals to B lymphocytes telling them where to find and attach to lymph nodes and bone marrow stroma; Drug inhibits PI3K; relapsed CLL in combination with rituximab; relapsed follicular B-cell NHL; relapsed small lymphocytic lymphoma | Diarrhea, fatigue, nausea, cough, pyrexia, abdominal pain, pneumonia, rash, laboratory abnormalities, CYP3A drug interactions Warnings: Severe cutaneous reactions, anaphylaxis, neutropenia, hepatotoxicity, severe diarrhea or colitis, serious infections, intestinal perforation, embryo-fetal toxicity |
| Proteasome inhibitors | Class effects: GI toxicity; embryo-fetal toxicity; CYP3A4 drug interactions; TLS; hepatotoxicity; thrombocytopenia | |
| Bortezomib (Velcade®)[70] (IV or subcutaneous injection) | 26S proteasome; multiple myeloma; mantle cell lymphoma | Nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, anorexia, CYP3A4 drug interactions Warnings: Peripheral neuropathy, hypotension, cardiac toxicity, pulmonary toxicity, PRES, GI toxicity, thrombocytopenia/neutropenia, TLS, hepatotoxicity, embryo-fetal toxicity |
| Carfilzomib (Kyprolis®)[71] (Intravenous) | 20S proteasome; relapsed or refractory multiple myeloma in combination with dexamethasone±lenalidomide, or as a single agent | Anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema (peripheral) Warnings: Cardiac toxicity, acute renal failure, TLS, pulmonary toxicity, pulmonary HTN, dyspnea, HTN, venous thrombosis, infusion reactions, hemorrhage, thrombocytopenia, hepatotoxicity, thrombotic microangiopathy, PRES, increased serious/fatal reactions in combination with melphalan/prednisone, embryo-fetal toxicity |
| Ixazomib (Ninlaro®)[72] | 20S proteasome (beta 5 subunit); multiple myeloma having received 1 prior therapy, given with lenalidomide and dexamethasone | Diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, back pain, CYP3A inducer drug interaction Warnings: Thrombocytopenia, CI toxicities, peripheral neuropathy, peripheral edema, cutaneous reactions, hepatotoxicity, embryo-fetal toxicity |
AML: Acute myeloid leukemia, ALK: Anaplastic lymphoma kinase, NSCLC: Nonsmall-cell lung cancer, RTK: Receptor tyrosine kinase, EGFR: Epidermal growth factor receptor, VEGF: Vascular endothelial growth factor, RCC: Renal cell cancer, PPES: Palmar-plantar erythrodysesthesia syndrome, CYP3A4: Cytochrome P enzyme system 3A4, RPLS: Reversible posterior leukoencephalopathy syndrome, RAI: Radioactive iodine, PDGF-R: Platelet-derived growth factor receptor, FGFR: Fibroblast growth factor receptor, CRC: Colorectal cancer, GIST: Gastrointestinal stromal tumor, pNET: Pancreatic neuroendocrine tumor, CLL: Chronic myelogenous leukemia, BCRs: B-cell receptors, CML: Chronic myeloid leukemia, ALL: Acute lymphoblastic leukemia, MDS: Myelodysplastic syndrome, TKIs: Tyrosine kinase inhibitor, TLS: Tumor lysis syndrome, BTK: Bruton's Tyrosine kinase, HDAC: Histone deacetylase, IDH2: Isocitrate dehydrogenase-2, mTOR: Mammalian target of rapamycin, PARP: Poly (ADP-ribose) polymerase, PI3K: Phosphatidylinositol 3-kinase, IV: Intravenous, MAPK: Mitogen-activated protein kinase, MCL: Mantle cell lymphoma, SLL: Small lymphocytic lymphoma, WM: Waldenstrom's macroglobulinemia, MZL: Marginal zone lymphoma, cGVHD: Chronic graft versus host disease, CDKs: Cyclin dependent kinase, HER 2: Human epidermal growth factor receptor-2, HR: Hormone receptor, ER: Estrogen receptor, PKC: Protein kinase C, SMO: Smoothened, RT: Radiotherapy, GI: Gastrointestinal, CTCL: Cutaneous T-cell lymphoma, PTLC: Peripheral T-cell lymphoma, CR: Complete responders, PR: Partial responders, NHL: Non-Hodgkin's Lymphoma, ILD: Interstitial lung disease, HTN: Hypertension, CPK: CPK: Creatine phosphokinase, LFTs: Liver function tests, MI: Myocardial infarction, TSH: Thyroid-stimulating hormone, URI: Upper respiratory infection, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, CHF: Congestive heart failure, G-6-PD: Glucose-6-phosphate dehydrogenase deficiency, HSRs: Hypersensitivity reactions, UTI: Urinary tract infection, AST: Aspartate aminotransferase, PRES: Posterior reversible encephalopathy syndrome, CI: Confidence interval, CK: Creatine kinase, QTc interval: Time during heart beat when there is ventricular activity, both depolarization and repolarization; it is measured as the distance between the beginning of the Q wave (beginning of QRS complex) to the end of the T wave on the ECG. The value is corrected for differences in heart rate (c). If the QTc interval is prolonged it increases the risk of ventricular arrhythmias, including Torsades de Pointes, and sudden death, ECG: Electrocardiogram, BR: bilirubin, CVA: Cerebrovascular accident, DVT: Deep venous thrombosis, P-pg: P-glycoprotein, a cellular drug efflux pump, PE: pulmonary embolus, PH: Philadelphia-chromosome, RET: -a proto-oncogene with a frequently mutated tyrosine kinase; RET=Rearranged during Transfection, AKTProtein-kinase B which plays a large role in glucose metabolism, apoptosis, cell proliferation, and transcription, ROS1: Proto-oncogene that encodes a protein kinase that is often mutated in cancer, IGF-1R: Insulin-like growth factor-1 is a transmembrane receptor that is implicated in certain cancers, FLT-3:Receptor tyrosine kinase important in hematologic stem/progenitor cell survival, and mutated in some patients with AML, EMLA4:stands for echinoderm micro-tubule associated protein-like 4, and genetically fuses with ALK to cause a certain type of NSCLC, NPM: Nucleophosmin is important in cellular functions, and the gene which makes it is mutated in some patients with AML, MET: Receptor tyrosine kinase that may be mutated in cancer, HGF: Hepatocyte growth factor aslo called scatter factor, which binds to MET and is often abnormal in cancer, HFSR: Hand Foot Skin Reaction, RAF: Protein kinase that is overexpressed in many cancers, SRC: Proto-oncogene whose tyrosine kinase is overexpressed in many cancers, BRAF: Proto-oncogene that is often mutated in cancer