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Oncology drugs

QuestionAnswer
What is adjuvant treatment? Curative treatment after a surgery
What is neoadjuvant treatment? Treatment before a surgery with curative intent
Hallmark chemotherapy treatment for NSCLC Platinum doublets (Cisplatin/Carboplatin + .....)
Pemetrexed Limit BMS by initiating Folic acid, B12, and dexamethasone a week prior to treatment
EGFR Antagonists Erlotinib, Afatinib Cetuximab
Erlotinib Take on an empty stomach (food increases toxicity) DDI with CYP 3A4/1A2 (1A2 is induced by smoking!!); antacids, H2 blockers, PPIs decrease absorption skin toxicity is good--treat like acne 1st line for EGFR mutations!
Crizotinib ALK mutation + NSCLC AE: visual disturbances
Bevacizumab VEGF AE: hemorrhage at site of tumor, HTN, proteinuria, thrombus; add as 3rd agent to cisplatin + paclitaxel
Treatment of SCLC Chemoradiation--chemo then XRT or XRT then chemo; cisplatin + etoposide
Stage II Colon Cancer Surgery --> 5-FU/Leucovorin (maybe add oxaliplatin if high risk)
Stage III Colon Cancer surgery --> FOLFOX 5-FU bolus and overnight + leucovorin + Oxaliplatin
Chemotherapy for metastatic colon cancer FOLFOX + bevacizumab (or cetuximab); FOLFIRI: 5-FU + leucovorin + irinotecan; Irinotecan (single agent)
What does 5-FU and Leucovorin together do for treating colon cancer? leucovorin makes the 5-FU work better; DPD degrades 5-FU, test for deficiency of DPD!
5-FU Continuous infusion vs bolus Continuous: more mucositis (can be limited with sucking on ice chips), diarrhea, hand&foot syndrome; Bolus: more myelosuppression
Other Colon Cancer regimens Capecitabine (single agent); CapeOX (capecitabine + oxaliplatin)
Capecitabine prodrug of 5-FU; take on full stomach and avoid antacids; AE: think of golf man: phototoxicity, diarrhea, hand&foot syndrome; 5-FU and capecitabine increase warfarin --> use LMWH
Oxaliplatin myelosuppression, moderately emetogenic, much less otoxicity and nephrotoxicity than cisplatin; Peripheral neuropathy exacerbated by the cold
Irinotecan early diarrhea (cholinergic storm) give atropine; late diarrhea give loperamide; metabolized into SN38
Cetuximab MAB that targets EGFR; mandatory k-RAS testing (patients with k-RAS mutations do not benefit from cetuximab or panitumumab) toxicities: rash (Avoid sun), serious infusion reactions, hypomagnesemia
Panitumumab MAB that targets EGFR; preferred over cetuximab when combined with FOLFOX; toxicities: rash, hypomagnesemia, less infusion reactions
Bevacizumab used in combination with chemotherapy ONLY in metastatic disease; GI perforations when used in colorectal cancers
Uses of Tamoxifen ER+/PR+ breast cancer any stage in pre- or post-menopausal women
AE of Tamoxifen hot flashes/flushing, thromboembolism, endometrial cancer
Strong 2D6 inhibitors that must be avoided with Tamoxifen use Fluoxetine, paroxetine, bupropion
Moderate 2D6 inhibitors that shouldn't be taken with Tamoxifen Duloxetine, sertraline, amiodarone, cimetidine, benadryl
Not/minimal 2D6 inhibitors that are safe with Tamoxifen use citalopram, escitalopram, venlafaxine
What Population of women can use Aromatase Inhibitors? Post-menopausal ONLY
What are the AIs? Anastrazole (1mg qd), Letrozole (2.5mg qd) , Exemestane (25mg qd)
AE of AI's hot flashes, arthralgias/myalgias, loss of BMD
Which have a high efficacy AIs or Tamoxifen? AIs
Early stage breast cancer treatment? Surgery --> local radiation --> hormonal therapy
Targeted Breast Cancer Therapy Trastuzumab for HER2 amplified disease
Adjuvant Regimens for Breast Cancer AC --> T (doxorubicin + cyclophosphamide --> paclitaxel)
Trastuzumab targets HER2; not to be given with anthracyclines, but unlike anthracyclines the HF it causes is transient and reversible
1st line for prostate cancer therapy androgen deprivation therapy--medical castration; GnRH agonists, GnRH antagonists, antiandrogens; testosterone < 50
GnRH agonists **DO NOT D/C these Leuprolide, Triptorelin, Goserelin, Histrelin
What happens during the first couple weeks of therapy with a GnRH agonist? Tumor flare! Consider 1-2 weeks of antiandrogen therapy
AE of GnRH agonists hot flashes, ED, decreased libido, bone pain (if bone mets)
Antiandrogen Bicalutamide, Enzalutmide; AE: hot flashes, decreased libido
Bicalutamide 50mg qd; AE: diarrhea, hematuria
Enzalutamide 160mg qd; AE: seizures, CNS effects, HA
ADT consequences Decreased BMD, metabolic syndrome, DM, CAD
What do you give men with prostate cancer and bone mets? Bisphosphonates + calcium and vitamin D supplementation; monitor SCr
Denosumab Treatment of ADT-induced bone loss and prevention of SREs
Abiraterone CYP17 inhibitor; TAKE ON EMPTY STOMACH (food increases AUC 10x) AE: mineralocorticoid excess (HTN, hypokalemia, edema) must take in combo with prednisone
Androgen Independent Prostate Cancer Docetaxel + Prednisone; AE: myelosuppression, edema, peripheral neuropathy
Localized Prostate Cancer Radiation + Prostatectomy often curative
Vemurafenib BRAFV600E (for mutation only) used in metastatic melanoma; increased risk of new skin cancer--frequent dermatologic evaluation
Dabrafenib BRAF TKI; high-fat meal will DECREASE absorption; insoluble at pH > 4
CTLA-4 "brake pedal" to immune system--block this for more activity against tumor cells
PD-1 prevents immune response to activating; block this and we can make immune system more effective at fighting tumor cells
Ipilimumab CTLA-4 inhibitor; BBW for immune-mediated response (entercolitis, hepatitis, dermatitis, neuropathy, endocrinopathy) treat with high dose corticosteroids and D/C until symptoms return to baseline and pred dose <7.5
Pembrolizumab and Nivolumab PD-1 inhibitors; immune-related toxicities
Dual Therapy in Metastatic Myeloma blocking multiple pathways is better, but still leads to inevitable resistance and greater toxicity
Asparaginase Usually part of the induction process for ALL; AE: hypersensitivity reactions, pancreatitis, hyperglycemia, coagulopathies (clots and bleeding)
Induction chemotherapy in ALL Kill everything, leukemia cells and bone marrow cells
Consolidation and Intensification chemotherapy in ALL eradicated leukemia cells; most regimens include high dose MTX
Maintenance chemotherapy in ALL daily 6-MP taken at NIGHT; if TPMT deficient reduce dose; avoid milk and allopurinol; OR weekly MTX therapy; OR monthly vincristine + corticosteroid blast
Risks of ALL treatment Induction phase: TLS (prevention with NS and allopurinol) infection risk (FN)
Induction Chemo for AML 7 days Cytarabine (cont. infusion) + 3 days anthracycline
Consolidation Chemo for AML HiDAC (high dose Ara-C--cytarabine) unique toxicities: cerebellar dysfunction, chemical conjunctivitis (corticosteroid eye drops)
Which antibiotic should not be chosen as a prophylactic drug for infectious complications in during leukemia chemotherapy? Bactrim--causes additional myelosuppression!
During which stage of AML therapy should you avoid the use of growth factors? Induction stage; during consolidation you can use growth factors; In ALL, there is no concern with growth factor use
When should you begin treatment for CLL? Only when needed; symtomatic, spleno/hepatomegaly, infectious complication, autoimmune complications
What are treatment option for CLL? Any combination of fludarabine, cyclophosphamide, rituximab; bendamustine (alkylating agent)
Rituximab Anti-CD20 MAB; Toxicities: infusion reactions (pretreat with APAP and benadryl)
Follicular (indolent) NHL localized disease; curable with radiation therapy alone
Advanced NHL radiation, chemotherapy (RCHOP/R-bendamustine), radioimmunotherapy
Aggressive (Diffuse Large B-cell Lymphoma) RCHOP = rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone
Very Aggressive (Burkitt's Lymphomas) alternate between A cycle and B cycle (resistance) with Rituximab throughout; A cycle = HyperCVAD (hyper-fractionated cyclophosphamide + vincristine + doxorubicin + dexamethasone); B cycle = high dose MTX, high dose cytarabine
Hodgkin's Lymphoma radiation + combination chemotherapy; late toxicities: leukemias, CV disease, pulm disease, solid tumors (in radiation field)
Chemotherapy for Hodgkin's ABVD = doxorubicin + bleomycin + vinblastine + dacarbazine (all agents given on days 1 & 15) NO dose delays or G-CSF regardless of low counts!
Multiple Myeloma Presentation C = hypercalcemia R = renal dysfunction A = anemia B = bone fractures
MM Treatment autologous stem cell transplant; chemotherapy for non-transplant candidates (melphalan + prednisone)
Melphalan alkylating agent only used in MM; harvest stem cells, kill all cells with melphalan, rescue with stem cells
Thalidomide AE: peripheral neuropathies, somnolence, neutropenia; thrombosis prophylaxis (ASA)
Lenalidomide AE: neutropenia; thrombosis prophylaxis (ASA)
Pomalidomide used after lenalidomide failure
Bortezomib proteasome inhibitor; AE: sensory neuropathy; Interaction with Green tea!
Treatment approach for CML first line TKI--imatinib, dasatinib, nilotinib; Allo HSCT if TKI failure
Imatinib BCR-ABL is the only issue with CML; Imatinib blocks BCR-ABL; Imatinib > combo therapy; resistance is NOT inevitable; 3A4 substrate; increase synthroid doses; take with food to minimize AE
Dasatinib blocks BCR-ABL; AE: pleural effusion; interaction with PPIs
Nilotinib active in most imatinib-resistant BCR-ABL mutations; AE: QT prolongation; take on empty stomach
CML and adherence Adherence is very important as this is a chronic disease!
GVHD Prophylaxis Regimen MTX + Tacrolimus
Calcineurin Inhibitors Cyclosporine, Tacrolimus; both limited by nephrotoxicity and metabolized by CYP3A4; nonmodified and modified cyclosporine formulations not interchangeable
Cyclosporine AE nephrotoxicity, HTN, tremor, hyperlipidemia, hypertriglyceridemia, gingival hyperplasia, hirsutism
Tacrolimus AE nephrotoxicity, HTN, tremor, hyperglycemia, HA (dose dependent), electrolytes abnormalities (hyperk, hypomag, hypophos)
Mycophenolate Mofetil stable in acidic environments (unlike MPA); first pass converts MFF --> MPA; AE: diarrhea
mTOR Inhibitors Sirolimus (macrolide); AE: myelosuppression, delayed wound healing, hypercholest and hypertriglyc, mouth ulcers
Treatment of acute GVHD methylprednisolone 1-2mg/kg/day
Induction therapy for solid organ transplant Methylprednisone, antimetabolite, calcineurin inhibitor (best), antibody therapy
Antibody therapies **these are all immunosuppressive** OKT-3 (muromonab-CD3), daclizumab and basiliximab, alemtuzumab; polyclonal: anti-thymocyte globulin
Antithymocyte Globlin comes from animals rabbit (RATG--thymoglobulin) preferred in kidney transplants;equine (atgam) preferred in aplastic anemia
Antithymocyte globulin safety myelosuppression (dose limiting)
Treatment of acute organ rejection increase immunosuppression (increase dose or add another agent); pulse corticosteroids
cell-cycle specific agents antimetabolites, vinca alkaloids, taxanes, etoposide, irinotecan, topotecan
cell-cycle nonspecific agents anthracyclines, platinums, alkylating agents, dacarbazine, nitrosureas (carmustine)
targeted agents MABs, hormonal (tamoxifen and AIs), TKIs (EGFR, VEGF, HER2, BCR-ABL)
Antimetabolites MTX, cytarabine, 5-FU, gemcitabine, fludarabine, 6-MP, hydroxyurea
Vinca alkaloids Vincristine, Vinblastine, Vinorelbine
Taxanes Paclitaxel, Docetaxel
Anthracyclines doxorubicin, daunorubicin, idarubicin, epirubicin
platinums cisplatin, carboplatin, oxaliplatin
Alkylating agents cyclophosphamide, ifosfamide, melphalan, busulfan, chlorambucil; cause secondary leukemia, teratogenic
Cyclophosphamide Prodrug activated in liver (2B6, 3A4/5) inducers increase toxicity; prevention of hemorrhagic cystitis in high doses ( bone marrow transplants) with fluids and mesna
Ifosfamide Prodrug activated in liver (2B6, 3A4/5) inducers increase toxicity; hemorrhagic more likely to occur--must give fluids and mesna ALWAYS!
Nitrosureas Carmustine, Lomustine; very lipophilic (cross BBB)
Dacarbazine prodrug metabolized to active MTIC (1A2)
Temozolomide prodrug chemically degraded to MTIC; 100% bioavailable
Cisplatin HIGHLY EMETOGENIC; nephrotoxic (give fluid before and after--add electrolytes), ototoxicity, neuropathies, electrolytes abnormalities (hypok, hypomag), minimal BMS
Carboplatin dosed based on renal function (calvert equation); toxicity: BMS
Oxaliplatin neuropathies exacerbated by cold temperatures
Doxorubicin red urine
Anthracycline Toxicities myelosuppression, irreversible cardiotoxicities (MUGA at baseline)
Mitoxantrone not an anthracycline (but close); NO free radical production (less cardiotoxicity than anthracyclines)
Taxane administration every 3 wks: more myelosuppression; every week: more neuropathy, nail changes
Paclitaxel hypersensitivity reactions due to vehicle (cremphor) premed with dex, benadryl, and H2 blocker
Docetaxel causes edema that must be pretreated with dex for 3 days (start prior to treatment)
What class of drugs are FATAL if given intrathecally? Vinca alkloids
Which vinca alkaloid does not cause myelosuppression? Vincristine
Cytarabine (Ara-C) standard doses cause myelosuppression and mucositis; high doses cause cerebellar toxicity and chemical conjunctivitis (corticosteroid eye drops)
6-MP coadministration with xanthine oxidase inhibitors increases toxicity
Fludarabine (purine analog) risk of opportunistic infections (AIDS-like), PCP prophylaxis (bactrim, inhaled pentamidine), HSV, VZV prophylaxis
MTX hydration and alkalinization of urine can prevent renal failure
High dose MTX therapy Leucovorin rescue; avoid drugs that may delay clearance: probenacid, sulfamethoxazole, penicillins, NSAIDs/ASA
Drugs that cause secondary leukemias etoposide, anthracyclines, alkylating agents
Bleomycin toxicity pulmonary fibrosis
Created by: simpsonan