general oncology from devita presentation

1. Dr. Chanchal

2. Tyrosine kinases (TKs)-
 Tyrosine kinase is an enzyme that helps in phosphorylation i.e
transfer of phosphate group from ATP to a protein inside the cell.
 Two groups of tyrosine kinases:
◦ Transmembrane protein receptors- Receptor tyrosine kinases
(RTKs).
◦ Non-receptor tyrosine kinases (NRTKs)- Acts as intracellular signal
transducers.
 When these proteins get mutated or overexpressed, their activation
may lead to increased proliferation, angiogenesis and inhibition of
apoptosis resulting in malignancy.

3. Receptor associated kinases:
◦ PDGFR
◦ EGFR- Epidermal growth factor receptor.
◦ IGF1R- Insulin like growth factor receptor-1
◦ SCR (c-Kit)- Soluble cytokine receptor.

4. Dysregulation of cell signaling networks-
•Uncontrolled cellular proliferation.
•Enhanced cellular survival.
•Enhance cellular motility.

5. Tyrosine kinase inhibitors (TKIs)-
 Small molecules (<900 daltons) that enters inside the cells to act on
intracellular TK domain.
 They have very high affinity for ATP binding pocket of the TKRs.
 Inhibit the transfer of a phosphate group from ATP to tyrosine residue.
 Acts cancerous as well as non-cancerous cells. Hence, resulting in
various side effects.
 Nomenclature- prefix + tinib.
 More then 30 TKI’s discovered till date.

7. Classification of TKI’s

8. Imatinib-
 Trade name-Gleevac.
 Available as 400 mg tablet (take large amount of water).
 Recommended dose -400-800 mg/day.
Mechanism of action-
 Binds to ATP pocket results in inhibition of substrate phosphorylation.
 Potent and selective inhibitor of the P210 Bcr-Abl tyrosine kinase.
 Inhibits PDGFR and c-Kit.

9. Mechanism of action

10. INDICATIONS
 CML with Ph+ {t(9,22)}.
 Newly diagnosed pediatric patients with Ph+ ALL.
 Chronic phase Ph+ CML in pediatric patients who have disease recurrence after
stem cell transplant or there is resistant to interferon-α.
 GIST expressing c-Kit (CD117)
◦ Unresectable and/or metastatic disease.
◦ As neo-Adjuvant therapy (6-12 months) in borderline resectable cases.
◦ Adjuvant therapy (1-3 yrs) following resection of localized disease with moderate to high risk
patients.
◦ No response in SDH deficient , non mutated kit & PDGFR (<5%) .
 DFSP- Unresectable, recurrent and metastatic (PDGFR +ve).
 MPD associated with PDGFR gene rearrangements.

11. Drug toxicity-
 Nausea and vomiting (40%–50%).
 Diarrhea (25%–30%).
 Occasional myalgias.
 Fluid retention- pleural effusion, ascites, pulmonary edema, and weight gain.
 Hypophosphatemia.
 Intra tumoral hemorrhage.
 Myelosuppression- Neutropenia and thrombocytopenia.
 Mild & transient elevation in serum transaminases (5 times of UL=STOP)
 Skin toxicity- bullous lesions, pustules & Stevens-Johnson syndrome.
 Insomnia, depression, and suicidal ideation- avoid use in previous H/O mental disorders.

12.  Trade name- Iressa.
 Classified as Signal transduction inhibitor TKI.
 Drug available as- 250 mg tablets.
Dose-
◦ 250 mg /day for locally advanced or metastatic NSCLC
◦ Dose may increased up to 500 mg if on concurrent CYP3A4 inducer.
Indications-
 Metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21
(L858R) substitution mutations.
 As a part of metronomic CT in SCC.

13. Mechanism of action-
 Selective EGFR tyrosine kinase
inhibitor-
◦ Inhibits EGFR autophosphorylation.
◦ Inhibits EGFR signaling.
◦ Inhibits mitogenic and antiapoptotic
signals involved in proliferation,
growth, metastasis & angiogenesis.

14. Drug toxicity-
 Hypertension- Patient may need antiHTN.
 Oral sores & mucositis.
 Pruritus, skin pustules & rashes.
 Conjunctivitis, blepharitis, and corneal erosions.
 Abnormal eyelash growth may occur in some patients.
 Mild-to-moderate elevations in serum transaminases levels.
 Hemoptysis and GI hemorrhage (rare).

15. Trade name- Tykerb.
 Classified as selective kinase inhibitor.
 Drug available as- 250 mg tablets.
 Targets EGFR/Her 1 and Her 2.
 Inhibit the downstream growth factor pathway( MAPK / PI3K/Akt)
 Crosses blood brain barrier.
Dose-
◦ 1250 mg PO daily on days 1–21 continuously in combination with capecitabine
1000 mg/m2 PO bid on days 1–14, with each cycle repeated every 21 days.
◦ Lapatinib (1500 mg PO/day)+ letrozole (2.5 mg PO/day).

16. Mechanism of action
Act on intracellular domain of both EGFR (HER-1) and HER 2 receptors

17. Indications-
 Used in combination with capecitabine in patients with HER2 +ve
advanced or MBC, who already recieved anthracycline, taxane and
trastuzumab based CT.
 Postmenpausal female with HER2 positive and ER positive MBC
in combination with letrozole.

18. Drug toxicity-
 Diarrhea (M.C= 65% ).
 Cardiac toxicity (5-7%) with reduction in LVEF.
◦ More common in first 9 weeks of therapy.
◦ More common in patients with previous h/o CAD.
◦ Monitor with ECG with QT measurement (> 500 msec withhold).
 Myelosuppression- anemia, thrombocytopenia or neutropenia.
 Fatigue and anorexia.
 Mild-to-moderate elevation of serum transaminases and serum bilirubin.
 Hand-foot syndrome and skin rash.
Important -
 Lapatinib should be taken 1 hour before or after a meal whereas capecitabine should
be taken within 30 minutes of meal.

19.  Trade name- Xalkori.
 Classified as Multiple receptor tyrosine kinases inhibitor.
 Drug available as- 250 mg capsules.
 Inhibits multiple receptor tyrosine kinases (RTKs)-
◦ ALK
◦ Hepatocyte growth factor receptor (c-Met).
◦ ROS1
◦ Recepteur d’originenantais (RON).
 Which results in inhibition of tumor growth, tumor angiogenesis, and
metastasis.

20. Indications-
 Treatment of locally advanced or metastatic NSCLC that is ALK–
positive.
 Treatment of patients with metastatic NSCLC that is ROS1-positive.
Dosage range-
 Recommended dose is 250 mg PO bid.

21. Drug toxicity-
 Hepatotoxicity with elevations in serum transaminases ( fatal outcomes were also
reported).
◦ Monitor regular LFT.
 Nausea, vomiting and diarrhea.
 Pulmonary toxicity-cough, dyspnea, fever, and pulmonary infiltrates.
◦ Stop the drug if pt develop treatment related pulmonary complications.
 Cardiac toxicity with QTc prolongation and sinus bradycardia.
◦ Avoid in patients with previous h/o CAD.
 Ocular side effects- diplopia, blurry vision, visual field defects, floaters/flashes,
visual brightness, and reduced visual acuity.
◦ Avoid work needed mental alertness.
 Peripheral , sensory and motor neuropathy (10%).

22. Trade name- Nexavar.
 Classified as multi receptor kinase inhibitor.
 Drug available as- 200 mg tablets.
 Targets multiple kinase receptors-
◦ Inhibits intracellular kinase- C-RAF, wild as well as mutant BRAF.
◦ Inhibits cell surface kinases- KIT, RET, VEGF-1,2,3 and PDGF –β.
 Dose-
◦ Recommended dose is 400 mg PO bid.
◦ Dose reduction may be required in Asian patients, as they appear to experience
increased toxicity to sorafenib.

23. Mechanism of action
C- raf & B-raf

24. Indications-
 Treatment of stage 4 & relapse in RCC (cat-2B,clear cell type).
 Treatment of unresectable & metastatic HCC (SHARP trail).
◦ Child pugh –A (Cat.1) & B7.
◦ ECOG-0-1.
Drug toxicity-
 Hypertension (6 weeks of starting therapy).
 Skin rash, Hand-foot skin reaction (30%).
 Bleeding complications- epistaxis,CVA etc.
 Wound-healing complications.
 Rarely- SCC skin (few case reported).

25. Trade name- Sutent.
 Classified as multi receptor kinase inhibitor.
 Drug available as- 12.5, 25 and 50 mg hard gelatin capsule.
 Multiple kinase receptors inhibitor-
◦ Platelet-derived growth factor receptors (PDGFR-α and PDGFR-β).
◦ Vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3).
◦ Stem cell factor receptor (Kit).
◦ Fms-like tyrosine kinase-3 (Flt-3).
◦ Colony-stimulating factor receptor type 1 (CSF-1R).
◦ Glial cell-line derived neurotrophic factor receptor (RET).

26. Indications-
 GIST with disease progression on or intolerance to Imatinib.
 Advanced Renal cell cancer (cat-1).
 Well-differentiated PNET-unresectable, progressive or metastatic
disease.
Dose-
 GIST and RCC:
◦ Recommended dose is 50 mg/day PO for 4 weeks followed by 2
weeks off.
◦ An alternative schedule is 50 mg/day PO for 2 weeks followed by 1
week off.
 PNET: Recommended dose is 37.5 mg/day PO continuously.

27. Drug toxicity-
 Hypertension ( 30%).
 Discoloration of the skin & hairs ( 30%).
 Bleeding complications- epistaxis, CVA etc.
 Stomatitis & altered taste.
 GI side effects- Abdominal pain, Diarrhea, Pancreatitis.
 Myelosuppression- Neutropenia and thrombocytopenia.
 Cardiac complications- LVF, CHF.
◦ Not to be use in patient cardiac event within 12 months.
◦ Discontinue drug if EF <50% or >20% fall pretreatment value.
 Adrenal insufficiency and Hypothyroidism.

28. Trade name- Caprelsa.
 Classified as Multi receptor kinase inhibitor.
 Drug available as- 100 and 300 mg tablets.
 Targets multiple kinase receptors-
◦ EGFR family.
◦ VEGFR
◦ Rearranged during transfection (RET).
◦ Protein tyrosine kinase 6 (BRK), Tie-2, EPH receptors, and Src family
members.
 Inhibition of various signaling pathways involved in proliferation, growth,
invasion/metastasis,and angiogenesis..

29. Indications-
 Symptomatic or progressive MTC-unresectable / locally advanced/ metastatic
disease.
Dose-
 Recommended dose is 300 mg PO daily and may be taken with or without food.
Drug toxicity-
 Mild-to-moderate skin reactions - rash, acne, dry skin, dermatitis, pruritis and rarely
Stevens-Johnson syndrome.
 Diarrhea, nausea and vomiting.
 Hypertension.
 Bleeding complications.
 Cardiac complications-QT prolongation, Torsades de Pointes rarely CHF..
 Pulmonary complications- ILD or Pneumonitis.
 CNS complications-seizures, headache, visual disturbances and altered mental
function.

30. Trade name- Zelboraf
 Classified as Multi receptor kinase inhibitor.
 Drug available as- 240 mg film coated tablets.
 Targets multiple kinase receptors-
◦ Inhibits mutant forms of BRAF serine-threonine kinase, including BRAF-
V600E.
◦ Mainly act by inactivation of MAPK signalling pathway.
◦ Does not inhibit wild-type BRAF and other Raf kinases ( ARAF and CRAF).
Dose range-
 Recommended dose is 960 mg PO bid.

31. Indications-
 Unresectable or metastatic melanoma with BRAF-V600E mutation.
 Not recommended for wild-type BRAF melanoma.
Drug toxicity-
 Cutaneous SCC and keratoacanthomas (up to 25% of patients within 7–8 wks).
 Skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
 Cardiac toxicity- with QTc prolongation.
 Hepatic toxicity- Elevations in serum bilirubin and transaminases.
 Photosensitivity.
 Opthalmologic side effects- uveitis, iritis, photophobia, and retinal vein occlusion.
 Fatigue.

32. Trade name- Votrient.
 Classified as Multi receptor kinase inhibitor of angiogenesis.
 Drug available as- 200 and 400 mg tablets.
Inhibits multiple kinase receptors of angiogenesis-
 VEGFR-1, VEGFR-2, VEGFR-3.
 PDGFR-α and PDGFR–β.
 Fibroblast growth factor receptor -FGFR-1 & 3.
 c-Kit, interleukin-2 receptor inducible T-cell kinase (Itk).
 Leukocyte-specific protein tyrosine kinase (Lck).
 Transmembrane glycoprotein receptor tyrosine kinase (c-Fms).

33. Indications-
 Advanced Renal cell carcinoma (Clear cell type, failure of cytokine
based CT)- (Cat.-1)
 Advanced soft tissue sarcoma (STS) where disease progress even
after CT.
◦ No documented benefit in adipocytic STS and GIST.
Dose-
 Recommended dose is 800 mg PO daily, taken atleast 1 hr before or 2
hr after meals.

34. Drug toxicity-
 Hypertension (50% of patients).
 Diarrhea, nausea,vomiting and abdominal pain.
 Increased risk of GI fistulas and/or perforations.
 Bleeding complications with hematuria, epistaxis, and hemoptysis.
 Deranged LFT- stop if AST >8 times of UL.
 Increased risk of arterial thrombolic events- MI, angina, TIA, and stroke.
 Proteinuria (8%).
 Myelosuppression & Hypothyroidism.

35. Drug interaction-
 Inhibitors CYP3A4- Erythromycin, clarithromycin, ketoconazole,
itroconazole, voriconazole and grape fruit juice (increase conc of
TKI’s)
 Inducer of CYP3A4- carbamazepine, dexamethasone, phenytoin,
refampicin (decrease conc of TKI’s)
 Decrease effectiveness of Thyroxine.
 PCM- increase risk of hepatotoxicity.
 Warfarin- Increase risk of bleeding.

37. Definition-
 Antibodies that are produced from a single clone of B cells is termed
as monoclonal antibody.

38. Production of MAb
(Hypoxanthine aminopterine thymidine)
(48-72 hrs)

41. Types of monoclonal antibodies

43. Ibritumomab tituxitan
Rituximab
Bivacizumab
Ado- trustuzumab Blinatumomab

44. Naked monoclonal antibodies-
Conjugated monoclonal antibodies-

45. Blinatumomab = anti CD 19 + anti CD 3
CD-19 expressed on precursor B- cells (Cancer cells)
CD-3 expressed on T-cell (Immune cells)

46.  Trade names- Herceptin.
Mechanism of action-
 Act on extracellular domain (subdomain 4) of the HER2/neu.
◦ HER2/neu overexpressed 25%–30% of breast cancers.
◦ 15- 20% of gastric cancers.
 Down-regulates expression of HER2/neu receptor.
 Inhibits HER2/neu intracellular signalling pathways.
 Induction of apoptosis of tumor cells.

47. Indications-
Patients with overexpression HER2/neu in-
 Metastatic breast cancer—First-line therapy in combination with
Paclitaxel in patients with overexpression HER2/neu.
 Early-stage breast cancer—as a part of adjuvant treatment.
 Metastatic gastric and GE junction adenocarcinoma in
combination with cisplatin and capecitabine or 5-FU.

48. Important points-
 Use with caution in patients with pre-existing cardiac dysfunction as
5-7% cases develop cardiac toxicities.
 Careful baseline assessment of cardiac function (LVEF) before as well
2 yr following completion of treatment.
 Trastuzumab should be stopped if >16% absolute decrease in LVEF
from a normal baseline value.
 Carefully monitor for infusion reactions, which typically occur
during or within 24 hours of drug administration.

49. Dose- Trastuzumab 4 mg/kg IV day 1 followed by 2 mg/kg IV
Weekly.
or
Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV
every 21 days.

50. PERTUZUMAB-
 Trade name- Perjeta.
 Pertuzumab targets the extracellular dimerization domain (subdomain II).
 Inhibits ligand‐induced tyrosine phosphorylation, and signal
downstreaming.
 More potent and comprehensive blockade of HER-2 driven signalling.
 Blocks ligand‐dependent heterodimerization of HER2 with other HER
members (HER1, HER3, and HER4) and homodimerization with other
HER2 receptors.
 Activate cells for destruction by immune system.

51. DOSE -Pertuzumab 840 mg IV day 1 of cycle 1 followed by 420 mg IV on
sequential Cycled every 21 days.
As per NCCN 2019,Pertuzumab + trastuzumab + docetaxel regimen is cat.1
treatment for HER-2-nue +ve MBC after relapse with previous TZ based CT.

52. Trade name- kadcyla.
 Conjugated Mab that is made up of
trastuzumab and small-molecule
microtubule inhibitor DM1.
 Receptor-mediated internalization and
lysosomal degradation, leading to
intracellular release of the DM1
molecule.
 Disruption of the microtubule network
resulting in cell-cycle arrest and
apoptosis.
 Inhibits HER2 downstream signaling
pathways.
 Immunologic-mediated mechanisms,
such as antibody-dependent cell-
mediated cytotoxicity (ADCC).

53. Indications-
 Her2-positive metastatic breast cancer who have received prior
treatment with trastuzumab and taxane based CT.
Dosage range-
 Recommended dose is 3.6 mg/kg iv every 3 weeks.
Important points-
 Stop the drug if the LVEF drops to <40% or >10% absolute
reduction from pretreatment baseline LVEF.
 Monitor LFTs- high risk of hepatotoxicity.
 Monitor for pulmonary symptoms. Stop the drug if patient develop
treatment-related pneumonitis or interstitial lung disease (ILD).

54. Bevacizumab (AVASTIN) :
 Bevacizumab is a recombinant humanized anti-VEGF-A MAb.
 FDA approved in 2004 for medical uses.
 t ½ = 20 days.
 Available as 100mg/ 4 ml or 400 mg/16 ml vial.
 Dose range : 5-15 mg /kg every 2-3 wkly regimen.
 It binds VEGF and prevents the interaction of VEGF to its
corresponding receptors on the surface of endothelial cells. Thus
inhibits angiogenesis.

55. Indications-
 First used in combination therapy with 5-FU based regimens for metastatic
colorectal cancer (mCRC).
 Used in combination with paclitaxel, doxorubicin or topotican for the treatment of
patients with platinum resistant ovarian or peritoneal cancer.
 Used in combination with interferon- α in metastatic RCC patients.
 Used in combination with carboplatin and paclitaxel for first line treatment of
unresectable,recurrent or metastatic non squamous non small cell lung cancer.
 Used in combination with cisplatin/paclitaxel or paclitaxel/topotecan for metastatic
or recurrent cervical cancer.
 Glioblastoma with progressive disease after prior therapy.

56. Adverse effects-
 Hypertension (10%)- patients may requires antiHTN treatment.
 Mild to moderate proteinuria (1%)- stop use if protienuria > 2gm /day.
 Increase risk of bleeding tendencies.
 Impaired surgical wound healing- avoid use in recent surgery atleast for
28 days.
 Thromboembolic events- More in pt age >65 yrs. May results in angina,
MI and stroke.
 Gut perforations- avoid use in pts with previous GI surgery or intervention.
 Ovarian failure.

57.  Trade names- Cyramza.
 Fully human MAb directed against VEGFR-2 and prevents binding of
VEGF-A, VEGF-C and VEGF-D ligands.
 Available as 100 mg /10 ml or 500 mg /50 ml vial.
Indications-
 Advanced mCRC used in patients with disease progression on or after prior
therapy with FOLFOX/XELOX plus bevacizumab. (RAISE trail)
 Advanced metastatic gastric or GE junction tumors in patients with
disease progression on or after fluoropyrimidine or platinum-containing CT.
 Advanced metastatic NSCLC in patients with disease progression on or
after platinum-containing CT.(REVEL trail).
◦ Can be used for squamous NSCLC in contrast to Bevacizumab.

58. Dosage range:
 mCRC is 8 mg/kg IV every 2 weeks in combination with FOLFIRI.
 Advanced gastric or GE junction adenocarcinoma is 8 mg/kg IV
every 2 weeks as monotherapy or in combination with paclitaxel.
 NSCLC is 10 mg/kg IV every 3 weeks in combination with
docetaxel.

59. Adverse effects-
 Hypertension (15-20%)- patients may requires antiHTN treatment.
 Mild to moderate proteinuria (1%)- stop use if protienuria > 2gm /day.
 Increase in bleeding tendency
 Impaired surgical wound healing- avoid use in recent surgery atleast
for 28 days.
 Thromboembolic events- More in pt age >65 yrs. May results in
angina, MI and stroke
 Gut perforations- avoid use in pts with previous GI surgery or
intervention
 Closely monitor thyroid function :Hypothyroidism.
Same as Bevacizumab

60.  Trade name- Rituxan.
 Available as 10 & 50 ml vial (10 mg/ml).

Mechanism of action-
 Chimeric anti-CD20 antibody present on B-lymphocytes.
 CD 20 is responsible for regulation of cell cycle initiation process.
 Induces apoptosis
 Downregulates B cell receptor
 Complement mediated cytotoxicity.
Dose range-
 NHL: Recommended dose for relapsed or refractory low-grade or follicular NHL is 375
mg/m2 IV on a weekly schedule for 4 or 8 weeks.
 Autoimmune disorderslikeRhumatoid arthritis: 1000mg i/v every 2 wk with 2 doses.

61. Indications-
 NHL with relapsed and/or refractory low-grade or follicular, B cell CD20+.
 Previously untreated diffuse large B-cell, CD20+.
 NHL in combination with CHOP or other anthracycline-based chemotherapy
regimens.
 Treatment of previously untreated and previously treated patients with CD20-
positive CLL.

62. Drug toxicity-
 Infusion-related symptoms- fever, chills, urticaria, flushing, fatigue,
headache, bronchospasm, rhinitis, dyspnea, angioedema, nausea and
Hypotension (1/2 to 3 hrs)
 Tumor lysis syndrome- hyperkalemia, hyperuricemia, hyperphosphatemia,
hypocalcemia, and renal insufficiency.
 Skin reactions- pemphigus, Stevens-Johnson syndrome, lichenoid
dermatitis.
 Arrhythmias and chest pain (during transfusion).
 Myelosuppression (rare).
Rituximab should NEVER be given by IV bolus

63.  Trade name- Erbitux.
 Classified as chimeric anti-EGFR Mab.
 Available as 100mg, 200 mg vial.
Mechanism of action-

64. Indications-
mCRC-
 EGFR-expressing mCRC
 Not recommended in patients with RAS mutations but can be used in wild type K-
RAS.
Head and neck cancer—
 Non – Nasopharyngeal recurrent, unresectable or metastatic H& N SCC. (cat-1 as
per NCCN 2019)
◦ Used as monotherapy in patients with disease progression after platinum-based
therapy.
◦ Use in combination with RT.
◦ Use in combination with platinum-based/ 5-FU based CT .

65. Dosage range-
 Loading dose of 400 mg/m2 IV administered over 120 minutes, followed by
maintenance dose of 250 mg/m2 IV given on a weekly basis.
 An alternative dosing schedule is 500 mg/m2 IV every 2 weeks with no need for a
loading dose.
Drug toxicity-
 Infusion-related reactions seen in 40-50% cases. use of prophylactic antihistamine
therapy.
 Skin reactions-Pruritus, dry skin and pustular skin lesions.
 Pulmonary toxicity- ILD manifested by increased cough, dyspnea and pulmonary
infiltrates (1%).
 Hypomagnesemia.
 Paronychial inflammation with swelling of the lateral nail folds of the toes and
fingers.

67. Classified as-
Anti–PD-1 -
◦ Nivolumab
◦ Pembrolizumab
Anti–PD-L1 -
◦ Atezolizumab
◦ Durvalumab
◦ Avelumab.
Anti-CTLA-4 -
◦ Ipilimumab
◦ Tremelimumab
Definition-
These are the novel drugs which act by alteration of expression and activity of various
immune checkpoint pathways ( TIGIT, TIM3, and LAG3) & other immune escape
mechanisms.

72. Drug can only be used if CPS≥ 1

74. Immune checkpoint inhibitor MAb
Drug toxicity-
 GIT- Diarrhea, colitis
 Hepatic- Elevated AST/ALT
 Endocrine- Hypophysitis , Hyperthroidism & Hypothyroidism .
 Cutaneous- Rash, pruritis and vitiligo.
 Respiratory- Pneumonitis & cough.
 General- Fatigue, nausea, vomiting, myalgia and arthralgia.

75. Thank u.....

76. •High levels of MSI (MSI-H) in CRC-
•About 15 %
•Right-sided
•Poorly differentiated
•Mucinous histology
•Good prognosis
•Poor response to 5FU

81.  ALK rearrangement: crizotinib, ceritinib, alectinib.
 EGFR mutation: afatinib, erlotinib, gefitinib, osimertinib.
 ROS1 rearrangement: crizotinib

82. Mechanism of action
Mechanism of action-
Multiple kinase receptors inhibitor
present on surface of tumor cells as
well as vessels-
◦ Platelet-derived growth factor receptors
(PDGFR-α and PDGFR-β).
◦ Vascular endothelial growth factor
receptors (VEGFR-1,VEGFR-2, and
VEGFR-3).
◦ Stem cell factor receptor (Kit).
◦ Fms-like tyrosine kinase-3 (Flt-3).