Treatment

Surgery For NSCLC

  • 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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Chemotherapy/Targeted Therapy For NSCLC

  • 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
First-line Therapy
  • 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
Subsequent Therapy
  • 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
Maintenance Therapy
  • Given after 4-6 cycles of chemotherapy for patients w/ tumor response or disease that did not progress
Continuation Maintenance Therapy
  • 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
Switch Maintenance Therapy
  • 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
Postoperative Therapy
  • 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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Radiotherapy For NSCLC

  • 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
Radical Radiotherapy
  • 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
Postoperative Radiotherapy
  • 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
Palliative Radiotherapy
  • 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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Surgery For SCLC

  • 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 For SCLC

  • 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
Initial therapy
  • 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
Subsequent Therapy
  • 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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Radiotherapy For SCLC

  • 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
Thoracic Irradiation
  • 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
Prophylactic Cranial Irradiation
  • 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
Palliative Radiotherapy
  • Recommended for patients w/ brain metastasis or those w/ localized symptomatic disease

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Palliative Care for Lung Cancer

  • Identify all patients who may benefit from palliative care & specialist referral should be done immediately
Pain
  • 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
Dyspnea, Cough & Compression Symptoms
  • 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
Superior Vena Cava (SVC) Obstruction
  • 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
Osseous Structural Impairment
  • 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
Brain Metastases
  • 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
Depression
  • Should always be assessed & managed

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Dosage Guidelines for NSCLC

1. Anti-Cancer Drugs for NSCLC - Combination Therapy1
  • 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
​1.1 Carboplatin + Gemcitabine2
  • 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
1.2 Carboplatin + Paclitaxel2
  • 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
1.3 Carboplatin + Paclitaxel + Bevacizumab2
  • 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
1.4 Cisplatin + Docetaxel2
  • 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
1.5 Cisplatin + Etoposide2
  • 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
1.6 Cisplatin + Gemcitabine2
  • 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
1.7 Cisplatin + Paclitaxel2
  • 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
1.8 Cisplatin + Pemetrexed2
  • 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
1.9 Cisplatin + Vinorelbine2
  • Vinorelbine: 30 mg/m2 IV on day 1, 8, 15 & 22
  • Cisplatin: 100 mg/m2 IV on day 1
  • Repeat cycle every 4 wk
2. Anti-Cancer Drugs for NSCLC - Monotherapy1
2.1 Cytotoxic Chemotherapy
2.1.1 Docetaxel

  • 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
2.1.2 Paclitaxel
  • 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
2.1.3 Pemetrexed
  • 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
2.1.4 Vinorelbine
  • 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

2.2 Monoclonal Antibody
2.2.1 Nivolumab

  • Adverse Reactions:
    • GI effects (abdominal pain, constipation, nausea); Resp effects (cough, dyspnea); Other effects (hyponatremia, inc AST/lipase, rash, fatigue, musculoskeletal pain)
  • Special Instructions:
    • Monitor liver enzymes, serum creatinine & thyroid function 
  • Dosage Guidelines:
    • 3 mg/kg IV infusion over 60 min 2 wkly

 

2.3 Tyrosine Kinase Inhibitors

2.3.1 Afatinib
  • 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
2.3.2 Crizotinib
  • 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
2.3.3 Erlotinib
  • 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
2.3.4 Gefitinib
  • 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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Dosage Guidelines for SCLC

1. Anti-Cancer Drugs for SCLC - Combination Therapy1
  • 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
1.1 Carboplatin + Etoposide (CE)2
  • 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
1.2 Cisplatin + Etoposide (PE)2
  • 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
1.3 Cyclophosphamide + Doxorubicin + Vincristine (CAV)2
  • 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
1.4 Cyclophosphamide + Doxorubicin + Vincristine + Etoposide (CAVE)2
  • 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
2. Anti-Cancer Drugs for SCLC - Monotherapy1
2.1 Topotecan
  • Adverse Reactions
    • CNS effects (fatigue, fever, headache); Dermatologic effects (alopecia, rash); GI effects (N/V, diarrhea, constipation, abdominal pain, anorexia, stomatitis); Hematologic effects (neutropenia, leukopenia, anemia, thrombocytopenia); Resp effect (dyspnea)
  • Special Instructions
    • Baseline neutrophil count >1500/mm3, re-treatment neutrophil ct >1500/mm3 baseline & re-treatment platelet count >100,000/mm3
    • Do not give replacement dose if patient vomits after therapy
  • Dosage Guidelines:2
    • 1.5 mg/m2 IV infusion over 30 min on day 1-5 or
    • 2.3 mg/m2 PO on day 1-5
    • Repeat cycle every 3 wk

1Other combination therapy & regimen variations are available. Please refer to specialist for specific treatment option
2Dosages of chemotherapy agents are calculated according to BSA in m2, unless otherwise specified

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All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated

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