Treatment

• Resectability of tumor should be fully assessed
• May offer the best chance of survival & possible cure in NSCLC patients
• Treatment of choice for stage I & II NSCLC
  • In the absence of medical contraindications to surgery, complete resection (ie lobectomy) w/ clear surgical margins should be achieved as much as possible
  • In patients w/ comorbidities who are not able to tolerate lobectomy, sublobar resection is recommended
  • Nodal dissection is preferred over simple intraoperative sampling for mediastinal LN
  • Sleeve lobectomy is recommended for total resection of centrally or locally advanced NSCLC
• Surgery in stage IIIA N2 lung cancer is controversial
  • Surgery is considered in resectable stage IIIA N0-1 tumors, followed by adjuvant chemotherapy
  • Usually not recommended if w/ involvement of N2; patient may undergo chemotherapy prior to surgery to decrease the tumor size, eliminate micrometastases & to improve patient’s tolerance to procedure
• Video-assisted thoracic surgery (VATS) is a less invasive & reasonable approach for patients w/ no anatomic or surgical contraindication

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• Recommended in patients w/ advanced disease [ie high risk stage IB patients (w/ poorly defined tumors, vascular invasion, wedge resection, minimal margins, >4 cm tumor, visceral pleural involvement, & regional LN that cannot be assessed) w/ negative nodal margin, stage IB patients w/ positive nodal margin, or patients w/ stage IIA, IIIA, IIIB, or IV irregardless of nodal margin status]
• Selection of systemic therapy is based on the histology of NSCLC
  • Histologic subtype & genetic alterations should be determined before therapy so that the best treatment can be selected
• Target therapy is potentially very effective in patients w/ specific gene mutations or rearrangements
• Platinum-based chemotherapy lengthens survival, improves symptom control & offers better quality of life
  • No specific platinum-based regimen is superior to the other

• Two drug regimen is preferred in patients w/ PS of 0-1 treatment-naive NSCLC
  • Addition of 3rd cytotoxic drug did not show increase in survival rate, except for Bevacizumab
  • Cisplatin-based regimens have been shown superior in patients w/ advanced & non-treatable disease, w/ 6-12 wk improvement in median survival & 10-15% improvement in 1 yr survival rates
  • Cisplatin or Carboplatin has been shown effective in combination w/ either Paclitaxel, Docetaxel, Gemcitabine, Vinorelbine, Etoposide, Vinblastine, Pemetrexed or albumin-bound Paclitaxel
  • In patients w/ nonsquamous NSCLC, Cisplatin + Pemetrexed regimen has been shown more effective & w/ reduced toxicity as compared w/ Cisplatin + Gemcitabine regimen
    • Cisplatin + Gemcitabine regimen has superior efficacy in patients w/ squamous histology
  • Cetuximab + Vinorelbine/Cisplatin may be an option for patients w/ PS 0-1
•  Chemotherapy w/ or w/o Bevacizumab is recommended in patients w/ advanced or recurrent NSCLC w/ PS of 0-1
  • Criteria for receiving Bevacizumab + chemotherapy: nonsquamous NSCLC & absence of hemoptysis
  • Bevacizumab added to standard chemotherapy regimen has been shown to prolong survival of patients w/ advanced lung cancer
  • Treatment option for patients w/ nonsquamous NSCLC or NSCSL NOS w/ PS 0-1 negative for ALK rearrangements or sensitizing EGFR mutations
  • Bevacizumab should be given until disease progression but should be used cautiously in patients w/ risk of thrombocytopenia & bleeding
• Single agent therapy or platinum-based regimen are alternative treatment options for elderly or patients w/ PS of 2 or w/ advanced or metastatic NSCLC adenocarcinoma
• Erlotinib or Gefitinib or Afatinib (in select patients) are recommended as 1st-line therapy in epidermal growth factor receptor (EGFR) mutation positive patients w/ advanced or metastatic NSCLC adenocarcinoma
  • Also indicated for use in patients w/ locally advanced or metastatic NSCLC after at least 1 prior failed chemotherapy regimen
• Crizotinib is recommended in select patients who have anaplastic lymphoma kinase (ALK) gene rearrangements
  • Shown to have very high response rates & significantly improves symptoms like pain, dyspnea or cough, & survival rate
  • May cause few side effects (eg increase in aminotransferase) or rare life-threatening pneumonitis
  • Also targets ROS1 gene rearrangements & MET amplification
• Ceritinib is recommended in patients w/ ALK positive metastatic NSCLC w/ disease progression after Crizotinib treatment

• Eg Docetaxel, Erlotinib, Gemcitabine, Nivolumab, Pemetrexed, or Ramucirumab + Docetaxel
• Recommended in patients w/ PS of 0-2 who have disease progression during or after 1st-line therapy
• Pemetrexed is recommended in patients w/ adenocarcinoma or large cell histology
  • Has similar median survival rate but less toxic than w/ Docetaxel
  • Recommended for patients w/ advanced non-squamous cell NSCLC previously given 1st-line therapy
• Erlotinib or Gefitinib is indicated as 2nd- or 3rd-line therapy for patients w/ PS of 0-2 w/ progressive disease
  • May also be considered for patients w/ PS of 3-4
  • Has been shown to significantly improve survival & delay the time of symptom deterioration
• Afatinib or Ceritinib may be used for patients w/ advanced or metastatic NSCLC
  • Afatinib is recommended in select patients who have sensitizing EGFR mutations
  • Ceritinib is recommended for patients w/ ALK gene rearrangements whose disease have progressed despite treatment w/ Crizotinib

• Given after 4-6 cycles of chemotherapy for patients w/ tumor response or disease that did not progress

• Utilizes at least 1 of the agents given as 1st-line
• Eg Bevacizumab, Cetuximab, Gemcitabine, Pemetrexed
  • Bevacizumab may be continued after 4-6 cycles of platinum-doublet chemotherapy + Bevacizumab
  • Cetuximab may be continued after 4-6 cycles of Cisplatin, Vinorelbine, & Cetuximab
  • Pemetrexed may be continued after 4-6 cycles of Cisplatin + Pemetrexed chemotherapy in patients w/ histologies other than squamous cell carcinoma
  • Gemcitabine may be continued after 4-6 cycles of platinum-doublet chemotherapy

• Utilizes other agent that is not part of the 1st-line regimen
• Eg Pemetrexed, Erlotinib, Docetaxel
  • Pemetrexed or Erlotinib used after 1st-line chemotherapy showed advantage in progression-free & overall survival
  • Pemetrexed may be started after 4-6 cycles of 1st-line platinum-doublet chemotherapy in patients w/ histologies other than squamous cell carcinoma
  • Erlotinib may be started after 4-6 cycles of 1st-line platinum-doublet regimen
  • Docetaxel may be started after 4-6 cycles of 1st-line platinum-doublet regimen in patients w/ squamous cell carcinoma

• Platinum-based chemotherapy is recommended for patients w/ PS of 0-1 who underwent complete resection for NSCLC stage II-IIIA

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• Used as an adjunct for patients w/ resectable lesions, as initial primary local treatment for medically unfit patients & w/ unresectable disease, & as a palliative modality for patients w/ advanced diseases
• Can be given to patients w/ stage IV NSCLC w/ extensive metastasis as a palliative care
• Concurrent thoracic irradiation & chemotherapy is superior to radiation alone or sequential chemotherapy followed by radiation in patients w/ locally advanced NSCLC

• Recommended for patients w/ stage I & II who are not fit for or do not consent to surgery
• Should be offered, in combination w/ chemotherapy, to patients w/ stage IIIA or IIIB NSCLC of good PS, in whom the tumor can be safely encompassed

• Consensus about treatment recommendations is lacking but may potentially be indicated in patients w/ involvement of mediastinum, multiple positive LN, extracapsular extension of LN, bulky LN, or w/ positive surgical margins

• Fractionated, higher dose is recommended for patients w/ thoracic symptoms & good PS but do not meet the requirements for radical radiotherapy

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• Considered only for patients w/ clinical stage I & in LD patients w/ sufficient pulmonary function & no evidence of metastases to mediastinal or supraclavicular lymph nodes
  • Patients w/ clinical stage in excess of T1-2, N0 do not benefit from surgery
• Lobectomy or pneumonectomy should be done followed by detailed dissection of the mediastinal LN
• Platinum-based adjuvant chemotherapy is recommended after surgery

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• Chemotherapy is an important part of recommended treatment for all patients w/ SCLC
• Adjuvant chemotherapy is advised in patients who underwent successful surgical resection
• Chemotherapy given simultaneously w/ thoracic radiotherapy is the recommended management for most LD SCLC patients w/ PS of 0-2
  • Also indicated for patients w/ LD whose pleural effusions are cytologically negative or indeterminate
• Chemotherapy alone is the recommended treatment for patients w/ ED SCLC w/o symptomatic sign
• Chemotherapy may be given before or after whole-brain radiotherapy in patients w/ ED & brain metastasis

• Single-agent or combination chemotherapy may be used in managing patients w/ SCLC
• Eg Cisplatin + Etoposide, Carboplatin +Etoposide, Irinotecan + Cisplatin, Irinotecan + Carboplatin
• Etoposide & Cisplatin regimen is the most commonly used initial combination chemotherapy
  • More effective & less toxic than alkylator + anthracycline-based regimens
  • Simultaneous use w/ thoracic radiotherapy is the recommended management for patients w/ LD but causes increased risk of esophagitis & pulmonary toxicity
• Carboplatin may be substituted to Cisplatin to decrease vomiting, neuropathy & nephropathy
  • Use in patients w/ LD has not been well studied & should only be given if Cisplatin is poorly tolerated or contraindicated
    • Showed similar therapeutic effect when used in patients w/ ED
    • Carboplatin + Irinotecan has been used as an alternative for treating patients w/ ED
• Maintenance or consolidation chemotherapy used beyond the standard 4-6 cycles produced minimal prolongation of duration of response w/o improvement in survival & poses greater risk of toxicity

• Provides important palliation in patients w/ SCLC but the effect depends on the time from initial therapy to relapse
  • If the interval is <3 mth, effect of regimen is <10%, which indicates a refractory SCLC; if >3 mth, expected effect is approximately 25%
  • Ifosfamide, Paclitaxel, Docetaxel, Gemcitabine, Irinotecan, Temozolomide, Topotecan can be considered in patients w/ PS of 0-2 that has disease that relapsed in <2-3 mth
  • Topotecan, Irinotecan, Cyclophosphamide + Doxorubicin + Vincristine, Gemcitabine, Paclitaxel, Docetaxel, oral Etoposide, Temozolomide,Vinorelbine may be used in patients w/ PS of 0-2 that has disease that relapsed in >2-3 mth up to 6 mth
  • In patients that has disease that relapsed for >6 mth, the original regimen should be used

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• Since SCLC is radiosensitive, radiotherapy is a vital part of treatment
  • Important for palliation of symptoms in ED SCLC patients w/ brain, epidural & bone metastasis
• Radiotherapy, once started, should proceed w/o interruption
• Advise patient to stop smoking prior to radiotherapy

• May be given to LD SCLC patients simultaneously w/ 1st or 2nd chemotherapy cycle
  • May also be given after completing chemotherapy if good response w/in the thorax is achieved
• After completion of chemotherapy, radiotherapy may be offered to ED SCLC patients provided a complete response on the distant sites & at least partial response w/in the thorax are achieved

• Aims to eradicate microscopic brain metastasis in asymptomatic patients
• Considered in patients w/ LD or ED SCLC of PS 0-2 in whom a complete response to primary treatment is achieved
• Should be incorporated w/in 3-5 wk of the last cycle of chemotherapy

• Recommended for patients w/ brain metastasis or those w/ localized symptomatic disease

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• Identify all patients who may benefit from palliative care & specialist referral should be done immediately

• Mild-moderate pain
  • Treat w/ Acetaminophen or nonsteroidal anti-inflammatory drug
• Severe pain
  • Treat w/ opioids
    • Meperidine is not used if pain medication will be given continuously; may cause dysphoria, agitation or seizure
    • May give medication for constipation prophylactically if opioid is used
  • Tricyclic antidepressants, anticonvulsants & neuropathic agents may be given to enhance the effect of pain medications
• Bone pain secondary to cancer metastasis
  • Radiotherapy is recommended for pain relief
  • Bisphosphonates (eg Pamidronate, Zoledronic acid) are advised together w/ radiotherapy
    • Bisphosphonates effectively relieve bone pain, treat hypercalcemia of malignancy & delay onset of bone disease progression

• Opioid & non-opioid antitussives may be given to the patient to reduce coughing
  • External beam radiotherapy is also an option
• Radiotherapy & stents may be considered in patients if there are breathlessness & hemoptysis due to the endobronchial tumor
• Relief of pleural effusion should be done primarily by thoracentesis
  • Recurrent pleural effusions should be managed w/ chest tube drainage & pleurodesis

• Chemotherapy is recommended for patients w/ symptomatic SVC obstruction secondary to SCLC
• Stent insertion &/or radiotherapy are recommended for patients w/ symptomatic SVC obstruction secondary to NSCLC & SCLC who do not respond to chemotherapy

• Orthopedic stabilization should be done prior to radiotherapy for patients at high risk for fracture due to osseous structural impairment
  • Preferred therapy for spinal cord compression & fractures compared to surgery

• Corticosteroids may be given to relieve headache, seizures & sensorimotor deficits
• Resection of isolated brain metastasis may be considered in NSCLC patients after complete tumor resection & w/ no metastasis found on other sites
  • Whole brain radiotherapy should follow removal of isolated single brain metastasis

• Should always be assessed & managed

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• Adverse Reactions
  • Bevacizumab
    • CV effects (hypertension, arterial thromboembolism); Hematologic effects (hemorrhage, neutropenia, leukopenia); CNS effects (reversible posterior leukoencephalopathy syndrome, pain, headache); Dermatologic effects (alopecia, exfoliative dermatitis); GI effects (GI perforation, hemorrhage, N/V, constipation, diarrhea); Other effects (infection, proteinuria, hypokalemia)
  • Carboplatin
    • CNS effects (pain, neurotoxicity, loss of vision w/ high dose); Endocrine effects (hyponatremia, hypomagnesemia, hypocalcemia, hypokalemia); GI effects (N/V, abdominal pain); Hematologic effects (leukopenia, anemia, neutropenia, thrombocytopenia); Hepatic effect (increased liver enzymes); Neuromuscular effect (weakness); Others (nephrotoxicity, allergy)
  • Cisplatin
    • CNS effect (neurotoxicity); GI effects (N/V); Hematologic effect (myelosuppression); Hepatic effect (increase in hepatic enzyme levels); Renal effect (nephrotoxicity); Otic effect (ototoxicity); Other effect (rarely anaphylaxis)
  • Docetaxel
    • CV effect (fluid retention); CNS effects (neuropathy, fever, neuromotor effects); Dermatologic effects (alopecia, cutaneous events, nail disorder); GI effects (stomatitis, diarrhea, N/V); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia, febrile neutropenia); Neuromuscular effects (weakness, myalgia); Resp effect (pulmonary events); Other effects (infection, hypersensitivity)
  • Etoposide
    • Dermatologic effect (alopecia); Endocrine effect (ovarian failure); GI effects (N/V, anorexia, diarrhea, mucositis); Hematologic effects (leukopenia, thrombocytopenia, anemia); Other effect (rarely anaphylaxis)
  • Gemcitabine
    • CV effects (peripheral edema, edema); CNS effects (pain, fever, somnolence); Dermatologic effects (rash, alopecia, pruritus); GI effects (N/V, constipation, diarrhea, stomatitis); Hematologic effects (anemia, leukopenia, neutropenia, thrombocytopenia, hemorrhage, myelosuppression); Hepatic effect (increased liver enzymes); Renal effects (proteinuria, hematuria, increase BUN); Resp effect (dyspnea); Other effect (infection)
  • Paclitaxel
    • CV effects (flushing, edema, hypotension, ECG abnormality); Dermatologic effects (alopecia, rash); GI effects (N/V, diarrhea, mucositis); Hematologic effects (neutropenia, leukopenia, anemia, bleeding, thrombocytopenia ); Hepatic effect (increase in alkaline phosphatase & AST); Local effects (inj site erythema, tenderness & swelling); Neuromuscular effects (peripheral neuropathy, arthralgia, weakness); Renal effect (increase in crea); Other effect (hypersensitivity)
  • Pemetrexed
    • CV effects (chest pain, edema); CNS effects (fatigue, fever, depression); Dermatologic effects (rash, desquamation); GI effects (anorexia, N/V, constipation, diarrhea, stomatitis); Resp effects (dyspnea, pharyngitis); Hematologic effects (neutropenia, leukopenia, anemia); Other effects (renal failure, infection)
  • Vinorelbine
    • CNS effect (fatigue); Hematologic effects (granulocytopenia, anemia); GI effects (constipation, N/V); Resp effects (dyspnea, bronchospasm); Dermatologic effect (alopecia); Hepatic effect (increased liver enzyme); Other effects (lower limb weakness, jaw pain, phlebitis)

• Special Instructions
  • Bevacizumab
    • Use w/ caution in patients w/ hypertension; monitor BP closely
    • Should not be given w/in 28 days of major surgery & only after complete healing of incision
    • Discontinue 28 days prior to elective surgery, in patients w/ nephrotic syndrome & w/ arterial thromboembolic events
  • Carboplatin
    • Taxane derivatives should be administered before platinum-based agents
    • Use w/ caution in patients w/ renal impairment
  • Cisplatin
    • Taxane derivatives should be administered before platinum-based agents
    • Hydrate patient w/ 1-2 L of IV fluid before & 24 hr after therapy
  • Docetaxel
    • Premedicate w/ corticosteroid prior & up to 5 days after therapy
    • Contraindicated in patients w/ ANC <1500 cells/mm³, AST >1.5 x upper normal limit (UNL), ALP >2.5 x UNL & bilirubin >UNL
  • Etoposide
    • Discontinue treatment if platelet count is <50,000/mm³, or ANC <500 cells/mm³
    • Use w/ caution in patients w/ hepatic & renal impairment
  • Gemcitabine
    • Use w/ caution in patients w/ renal & hepatic impairment
  • Paclitaxel
    • Contraindicated in patients w/ ANC <1,500 cells/mm³
    • Premedicate w/ Dexamethasone (20 mg PO or IV at 12 & 6 hr or 14 & 7 hr prior), Diphenhydramine (50 mg IV 30-60 min prior) & IV H₂ antagonist (30-60 min prior)
  • Pemetrexed
    • Pretreatment w/ Dexamethasone 4 mg PO 12 hrly 1 day before, during & 1 day after therapy is recommended
    • Folic acid supplementation, 350-1,000 mcg/day 1 wk before, during & 21 days after therapy is required
    • Vit B12 supplementation, 1000 mcg IM, 1 dose 1 wk before treatment & every 3 cycles thereafter is also required
  • Vinorelbine
    • Follow IV dose w/ 75-125 mL saline or D5W

• Regimen 1:
  • Gemcitabine: 1000 mg/m² IV infusion over 30 min on day 1, 8 & 15
  • Carboplatin³: AUC of 5 IV infusion over 30 min on day 1
  • Repeat cycle every 4 wk
• Regimen 2:
  • Gemcitabine: 1000-1100 mg/m² IV infusion over 30 min on day 1 & 8
  • Carboplatin³: AUC of 5 IV infusion over 30 min on day 8
  • Repeat cycle every 4 wk

• Paclitaxel: 200 mg/m² IV infusion over 3 hr on day 1, followed by
• Carboplatin³: AUC of 6 IV infusion over 30 min on day 1
• Repeat cycle every 3 wk

• Paclitaxel: 200 mg/m² IV infusion over 3 hr on day 1, followed by
• Carboplatin³: AUC of 6 IV infusion over 30 min on day 1, followed by
• Bevacizumab: 15 mg/kg IV on day 1
• Repeat cycle every 3 wk

• Docetaxel: 75 mg/m² IV infusion over 1 hr on day 1, followed by
• Cisplatin: 75 mg/m² IV infusion over 30 min on day 1
• Repeat cycle every 3 wk

• Cisplatin: 100 mg/m² IV infusion on day 1, followed by
• Etoposide: 100 mg/m² IV infusion on days 1-3
• Repeat cycle every 4 wk

• Gemcitabine: 1250 mg/m² IV infusion over 30 min on day 1 & 8
• Cisplatin: 75 mg/m² IV infusion over 30 min on day 1
• Repeat cycle every 3 wk

• Cisplatin: 75 mg/m² IV infusion over 30 min on day 1, followed by
• Paclitaxel: 135 mg/m² IV infusion over 24 hr
• Repeat cycle every 3 wk

• Pemetrexed: 500 mg/m² IV infusion over 10 min
• Cisplatin: 75 mg/m² IV infusion over 30 min on day 1
• Repeat cycle every 3 wk

• Vinorelbine: 30 mg/m² IV on day 1, 8, 15 & 22
• Cisplatin: 100 mg/m² IV on day 1
• Repeat cycle every 4 wk

• Adverse Reactions:
  • CV effect (fluid retention); CNS effects (neuropathy, fever, neuromotor effects); Dermatologic effects (alopecia, cutaneous events, nail disorder); GI effects (stomatitis, diarrhea, N/V); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia, febrile neutropenia); Neuromuscular effects (weakness, myalgia); Resp effect (pulmonary events); Other effects (infection, hypersensitivity)
• Special Instructions:
  • Premedicate w/ corticosteroid prior & up to 5 days after therapy
  • Contraindicated in patients w/ ANC <1500 cells/mm³, AST >1.5 x upper normal limit (UNL), ALP >2.5 x UNL & bilirubin >UNL
• Dosage Guidelines:²
  • 75 mg/m² IV infusion over 1 hr on day 1, every 3 wk

• Adverse Reactions:
  • CV effects (flushing, edema, hypotension, ECG abnormality); Dermatologic effects (alopecia, rash); GI effects (N/V, diarrhea, mucositis); Hematologic effects (neutropenia, leukopenia, anemia, bleeding, thrombocytopenia ); Hepatic effect (increase in alkaline phosphatase & AST); Local effects (inj site erythema, tenderness & swelling); Neuromuscular effects (peripheral neuropathy, arthralgia, weakness); Renal effect (increase in crea); Other effect (hypersensitivity)
• Special Instructions:
  • Contraindicated in patients w/ ANC <1,500 cells/mm³
  • Premedicate w/ Dexamethasone (20 mg PO or IV at 12 & 6 hr or 14 & 7 hr prior), Diphenhydramine (50 mg IV 30-60 min prior) & IV H₂ antagonist (30-60 min prior)
• Dosage Guidelines:²
  • 175 mg/m² IV infusion over 3 hr every 3 wk

• Adverse Reactions:
  • CV effects (chest pain, edema); CNS effects (fatigue, fever, depression); Dermatologic effects (rash, desquamation); GI effects (anorexia, N/V, constipation, diarrhea, stomatitis); Resp effects (dyspnea, pharyngitis); Hematologic effects (neutropenia, leukopenia, anemia); Other effects (renal failure, infection)
• Special Instructions:
  • Pretreatment w/ Dexamethasone 4 mg PO 12 hrly 1 day before, during & 1 day after therapy is recommended
  • Folic acid supplementation, 350-1,000 mcg/day 1 wk before, during & 21 days after therapy is required
  • Vit B12 supplementation, 1000 mcg IM, 1 dose 1 wk before treatment & every 3 cycles thereafter is also required
• Dosage Guidelines:²
  • 500 mg/m² IV infusion over 10 min on day 1, every 3 wk

• Adverse Reactions:
  • CNS effect (fatigue); Hematologic effects (granulocytopenia, anemia); GI effects (constipation, N/V); Resp effects (dyspnea, bronchospasm); Dermatologic effect (alopecia); Hepatic effect (increased liver enzyme); Other effects (lower limb weakness, jaw pain, phlebitis)
• Special Instructions:
  • Follow IV dose w/ 75-125 mL saline or D5W
• Dosage Guidelines:²
  • 25-30 mg/m² IV infusion every 7 days

• Adverse Reactions:
  • GI effects (diarrhea, decreased appetite); Dermatologic effects (dry skin, pruritus, dermatitis acneiform, rash, paronychia); Other effects (epistaxis)
• Special Instructions:
  • Contraindicated in patients w/ galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  • Use w/ caution in patients w/ renal/hepatic impairment, interstitial lung disease, history of keratitis, ulcerative keratitis or severe dry eyes
  • Monitor left ventricular function in patients w/ cardiac risk factors
  • Take at least 1 hr before or 3 hr after meals
• Dosage Guidelines:
  • 40 mg PO 24 hrly

• Adverse Reactions:
  • GI effects (diarrhea, N/V, constipation); Resp effects (pneumonia, pulmonary embolism, dyspnea); Other effects (vision disorder, edema, fatigue, decreased appetite, neuropathy, dizziness, dysgeusia, increased ALT & neutropenia)
• Special Instructions:
  • Assess for ALK positive NSCLC
  • Contraindicated in patients w/ hepatic impairment
• Dosage Guidelines:
  • 250 mg PO 12 hrly

• Adverse Reactions:
  • CNS effects (fatigue, anorexia); GI effects (diarrhea, N/V, stomatitis, abdominal pain, GI perforation); Hepatic effects (increased hepatic enzyme levels & bilirubin); Dermatologic effects (rash, pruritus, dry skin, keratitis); Resp effects (dyspnea, cough); Other effects (conjunctivitis, keratoconjunctivitis sicca, infection)
• Special Instructions:
  • Administer 1 hr before & 2 hrs after meal
  • Use w/ caution in patients on anticoagulant medication, elevated INR, & bleeding tendency
• Dosage Guidelines:
  • 150 mg/day PO

• Adverse Reactions
  • CNS effect (anorexia); Dermatologic effects (rash, pruritus, skin dryness, nail disorder, alopecia); GI effects (diarrhea, N/V, stomatitis); Other effects (conjunctivitis, dyspnea); Hepatic & renal toxicity
• Special Instructions
  • Should only be used in cancer patients who already have taken the medication, otherwise, physician should use other option
• Dosage Guidelines:
  • 250 mg/day PO

¹Other combination therapy & regimen variations are available. Please refer to specialist for specific treatment option
²Dosages of chemotherapy agents are calculated according to body surface area (BSA) in m², unless otherwise specified
³Carboplatin dosage in mg = area under concentration-time curve (AUC) of 6 (or 5) = (GFR + 25) x 6 (or 5); & GFR = {1.2 x (140-age in yr) x (BW in kg) / serum creatinine in µmol/L} x 0.85 (for females only)

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• Adverse Reactions
  • Carboplatin
    • CNS effects (pain, neurotoxicity, loss of vision w/ high dose); Endocrine effects (hyponatremia, hypomagnesemia, hypocalcemia, hypokalemia); GI effects (N/V, abdominal pain); Hematologic effects (leukopenia, anemia, neutropenia, thrombocytopenia); Hepatic effect (increased liver enzymes); Neuromuscular effect (weakness); Others (nephrotoxicity, allergy)
  • Cisplatin
    • CNS effect (neurotoxicity); GI effects (N/V); Hematologic effect (myelosuppression); Hepatic effect (increase in hepatic enzyme levels); Renal effect (nephrotoxicity); Otic effect (ototoxicity); Other effect (rarely anaphylaxis)
  • Cyclophosphamide
    • Dermatologic effect (alopecia); Endocrine effects (amenorrhea, sterility); GI effects (N/V, anorexia, diarrhea); GUT effect (acute hemorrhagic cystitis); Hematologic effect (leukopenia)
  • Doxorubicin
    • CV effects (AV block, bradycardia, ECG abnormality); Dermatologic effect (alopecia); GI effects (N/V, mucositis, GI ulcers, anorexia, diarrhea); GU effect (red discoloration of urine); Hematologic effects (leukopenia, thrombocytopenia, anemia); Endocrine effects (amenorrhea, hyperuricemia)
  • Etoposide
    • Dermatologic effect (alopecia); Endocrine effect (ovarian failure); GI effects (N/V, anorexia, diarrhea, mucositis); Hematologic effects (leukopenia, thrombocytopenia, anemia); Other effect (rarely anaphylaxis)
  • Vincristine
    • Dermatologic effect (alopecia); CV effects (orthostatic hypotension or hypertension); CNS effects (depression, headache, insomnia, fever); GI effects (anorexia, bloating, paralytic ileus)
• Special Instructions
  • Carboplatin
    • Taxane derivatives should be administered before platinum-based agents
    • Use w/ caution in patients w/ renal impairment
  • Cisplatin
    • Taxane derivatives should be administered before platinum-based agents
    • Hydrate patient w/ 1-2 L of IV fluid before & 24 hr after therapy
  • Cyclophosphamide
    • Increase fluid intake (2 L/day) during & 1-2 days after therapy
    • Use w/ caution in patients w/ hepatic & renal impairment
  • Doxorubicin
    • Flush w/ 5-10 mL of IV soln before & after giving drug
    • Contraindicated in patients w/ recent MI, severe myocardial insufficiency, severe arrhythmia, baseline neutrophil count <1,500/mm³, severe hepatic impairment
  • Etoposide
    • Discontinue treatment if platelet count is <50,000/mm³, or ANC <500 cells/mm³
    • Use w/ caution in patients w/ hepatic & renal impairment
  • Vincristine
    • Give prophylaxis for constipation
    • Use w/ caution in patients w/ hepatic impairment & pre existing neuromuscular disease

• Carboplatin:
  • 300 mg/m² IV infusion over 30 min on day 1
• Etoposide:
  • 80-100 mg/m² IV infusion over 30 min on day 1-3
• Repeat cycle every 3 wk

• Etoposide:
  • 100 mg/m² IV infusion over 30 min on day 1-3
• Cisplatin:
  • 80 mg/m² IV infusion over 30 min on day 1
• Repeat cycle every 3 wk

• Cyclophosphamide:
  • 1000 mg/m² IV on day 1, every 3 wk
• Doxorubicin:
  • 45 mg/m² IV on day 1
• Vincristine:
  • 1.4 mg/m² IV on day 1
  • Max dose: 2 mg
• Repeat cycle every 3 wk

• Cyclophosphamide:
  • 750 mg/m² IV on day 1
• Doxorubicin:
  • 50 mg/m² IV on day 1
• Vincristine:
  • 1.4 mg/m² IV on day 1
  • Max dose: 2 mg
• Etoposide:
  • 100 mg/m² IV infusion over 30 min on day 1-3
• Repeat cycle every 3 wk