• Users Online: 192
  • Print this page
  • Email this page


 
 
Table of Contents
PROFESSIONAL RESOURCE
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 19-40

Adjuvant chemotherapy protocols for lung cancer


1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Rajiv Gandhi Hospital, New Delhi, India
3 Department of Medical Oncology, Action Cancer Hospital, New Delhi, India

Date of Web Publication12-Dec-2018

Correspondence Address:
Dr. Sameer Shrirangwar
Plot No. 82, “Shubham Regency”, Flat No. 101, Canal Road, Ramdaspeth, Nagpur - 440 012, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_8_18

Get Permissions


How to cite this article:
Shrirangwar S, Sharma M, Jandyal S, Kate S. Adjuvant chemotherapy protocols for lung cancer. Cancer Res Stat Treat 2018;1:19-40

How to cite this URL:
Shrirangwar S, Sharma M, Jandyal S, Kate S. Adjuvant chemotherapy protocols for lung cancer. Cancer Res Stat Treat [serial online] 2018 [cited 2019 Feb 23];1:19-40. Available from: http://www.crstonline.com/text.asp?2018/1/1/19/247333



We have listed some of the commonly used protocols for adjuvant chemotherapy in lung cancer. This is not a comprehensive list. The protocols are not arranged in order of preference, but alphabetically.


  Table of Contents Top





  Lung – paclitaxel Carboplatin Protocol Top





  Please Enter Exact Total Doses of Each Cycle in Milligrams Top




Oral medication

  • Cap. Aprepitant 125 mg PO day 1 and 80 mg PO day 2 and 3
  • Tablet Olanzapine 5 mg PO BD day 1 to day 4
  • Tablet Tramadol 50 mg PO BD X 3 days.




Extravasation

  • Paclitaxel: Vesicant
  • Carboplatin: Nonvesicant.


Antiemetics

  • Paclitaxel: Low emetogenic
  • Carboplatin: Moderate emetogenic.


Interactions



  • The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution should be exercised when administering paclitaxel concomitantly with known substrates or inhibitors of the cytochrome P450 isoenzymes CTP2C8 and CYP3A4.
  • Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g. midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g. atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.
  • Caution should also be exercised when paclitaxel is concomitantly administered with known substrates (e.g. repaglinide and rosiglitazone), inhibitors (e.g., gemfibrozil), and inducers (e.g., rifampin) of CYP2C8.
  • Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.


Drug-food

No documented interactions.

Special instruction for food:

  1. Small frequent meals □
  2. Fruits after washing □
  3. Canned/packed juice □
  4. Hygienic diet □


2) Carboplatin

  • Aminoglycoside antibiotics: increased risk of nephrotoxicity and ototoxicity
  • Clozapine: increased risk of agranulocytosis, avoid concomitant use
  • Diuretics: increased risk of nephrotoxicity and ototoxicity
  • Nephrotoxic drugs: increased nephrotoxicity; not recommended -Phenytoin: reduced absorption of the antiepileptic.


Dose modifications

1. Paclitaxel

  • Dosage in renal failure: No dose adjustment required
  • Dosage in hepatic failure:




  • Doses with peripheral neuropathy -


If a Grade 2 neuropathy (paresthesia interfering with function, but not interfering with ADL) or worse develops, paclitaxel dose should be reduced to 160 mg/m2. If progressive neuropathy is observed after this dose reduction, then treatment with paclitaxel should be discontinued.

2) Carboplatin:











  1. Felip E, Rosell R, Maestre JA, Rodríguez-Paniagua JM, Morán T, Astudillo J, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol 2010;28:3138-45.
  2. TAXOL (paclitaxel) INJECTION. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020262s049lbl.pdf.
  3. PARAPLATIN Label. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf.
  4. Paclitaxel and Carboplatin in NSCLC (Non-small cell lung cancer), South East London Cancer Network, NHS. http://www.londoncanceralliance.nhs.uk/media/40047/nsclc_paclitaxel_carbo_protocol_v1.0.pdf.



  Lung – paclitaxel Cisplatin Protocol Top





  Please Enter Exact Total Doses of Each Cycle in Milligrams Top




Oral medications

  1. Capsule Aprepitant 125 mg PO day1 and 80 mg PO day 2 and 3
  2. Tablet Dexamethasone 4 mg PO BDX 3 days day 2–4
  3. Tablet Ranitidine 150 BD D2-D4
  4. Tablet Olanzapine 5 mg BD D1-4
  5. Tablet Tramadol 1 BD D1-D4




INTERACTIONS:[2],[3]



  • The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution should be exercised when administering paclitaxel concomitantly with known substrates or inhibitors of the cytochrome P450 isoenzymes CTP2C8 and CYP3A4.
  • Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.
  • Caution should also be exercised when paclitaxel is concomitantly administered with known substrates (e.g., repaglinide and rosiglitazone), inhibitors (e.g., gemfibrozil), and inducers (e.g., rifampin) of CYP2C8.
  • Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.


Drug-Food

No documented interactions

Special instruction for food:

  1. Small frequent meals □
  2. Fruits after washing □
  3. Canned/Packed Juice □
  4. Hygienic diet □




Dose modifications

1) Paclitaxel:

  • Dosage in renal failure: No dose adjustment required
  • Dosage in hepatic failure:




  • Dosage with peripheral neuropathy


If a Grade 2 neuropathy (paresthesia interfering with function, but not interfering with ADL) or worse develops, paclitaxel dose should be reduced to 160 mg/m2. If progressive neuropathy is observed after this dose reduction, then treatment with Paclitaxel should be discontinued.



2) Cisplatin:

  • Dosage in hepatic failure: No adjustment required
  • Dosage in renal failure:


In general, renal function should have normalized before patients are retreated. If continued treatment is considered to be mandatory, the following dose modifications could be considered at the physician's discretion.



  • Dosage in elderly:


  • Geriatric patients may be at higher risk of developing nephrotoxicity, ototoxicity/neurotoxicity, or hematologic adverse effects with cisplatin.

  • Children:


Dosage and safety not definitively established. Children maybe at higher risk of ototoxicity.







  1. Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, et al. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: A cooperative multinational trial. Ann Oncol 2002;13:1539-49.
  2. TAXOL (paclitaxel) INJECTION. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020262s049lbl.pdf.
  3. Cisplatin drug monograph, CCO Formulary; August, 2016. Available from: https://www.cancercareontario.ca/en/drugformulary/drugs/cisplatin.



  Lung – pemetrexed Carboplatin Protocol Top





  Please Enter Exact Total Doses of Each Cycle in Milligrams Top




  1. Tablet folic acid 2.5 mg OD 1 week before then daily until 3 weeks post chemo
  2. Tablet Dexamethasone 4 mg BD day 0–4
  3. Capsule Aprepitant 125 mg PO on day 1, then 80 mg PO OD on day 2 and day 3
  4. Tablet Ranitidine 150 mg BD day 0–4




Skin rash has been reported in patients not pre-treated with a corticosteroid. Standard therapy to reduce the incidence and severity of skin reactions includes dexamethasone 4 mg PO twice daily given the day before, the day of, and the day after pemetrexed administration.[2]

Treatment-related toxicity, including bone marrow suppression, diarrhea, and mucositis, are significantly reduced by supplementing with folic acid and Vitamin B12. Patients should take 0.4 mg oral folic acid (0.35 – 1 mg) daily beginning 1 week before and continuing daily until 3 weeks after the last pemetrexed dose. At least 5 daily doses must be taken during the 7 days before the start of therapy. Patients should also receive Vitamin B12 1000 mcg IM injection 1 week before pemetrexed therapy. This should be repeated every 9 weeks until 3 weeks after the last pemetrexed dose.[2]

Interactions:[2],[3],[4],[5]



Drug-food

Pemetrexed

No documented interactions

Special instruction for food:

  1. Small frequent meals □
  2. Fruits after washing □
  3. Canned/packed Juice □
  4. Hygienic diet □


2) Carboplatin -

  • Aminoglycoside antibiotics: increased risk of nephrotoxicity and ototoxicity
  • Clozapine: increased risk of agranulocytosis, avoid concomitant use
  • Diuretics: increased risk of nephrotoxicity and ototoxicity


  • Nephrotoxic drugs: increased nephrotoxicity; not recommended
  • Phenytoin: reduced absorption of the antiepileptic.


Anti-emetics: highly emetogenic

Extravasation: non vesicants

Laboratory monitoring and dose reduction/discontinuation recommendations.[4]



If there are two or more delays, a 25% dose reduction of both carboplatin and pemetrexed may be considered.



If EDTA-GFR or calculated creatinine clearance <20ml/min, carboplatin is contraindicated.

  • Hepatic impairment:


No dose adjustments indicated. Pemetrexed is primarily renally excreted unchanged. However, it has not been studied in patients with hepatic impairment.



If a patient suffers any Grade 3 or 4 toxicity after 2 dose reductions, treatment must be reviewed.





  1. Zhang L, Ou W, Liu Q, Li N, Liu L, Wang S, et al. Pemetrexed plus carboplatin as adjuvant chemotherapy in patients with curative resected non-squamous non-small cell lung cancer. Thorac Cancer 2014;5:50-6.
  2. ALIMTA (pemetrexed disodium) Injection. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021462s021lbl.pdf.
  3. PARAPLATIN Label. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf.
  4. Lung Pathway Group – Pemetrexed in Non-Small Cell Lung Cancer (NSCLC). Available from: http://rmpartners.cancervanguard.nhs.uk/wp-content/uploads/2017/03/lca-lung-protocol-pemetrexed-1.pdf.
  5. Paclitaxel and Carboplatin in NSCLC (Non-small cell lung cancer), South East London Cancer Network, NHS. http://www.londoncanceralliance.nhs.uk/media/40047/nsclc_paclitaxel_carbo_protocol_v1.0.pdf.



  Lung – pemetrexed Cisplatin Protocol Top





  Please Enter Exact Total Doses of Each Cycle in Milligrams Top




  1. Tablet folic acid 2.5 mg mg OD 1 week before then daily until 3 weeks post chemo
  2. Tablet Dexamethazone 4 mg BD day 0–4
  3. Capsule Aprepitant 125 mg PO on day 1, then 80 mg PO OD on day 2 and day 3
  4. Tablet Ranitidine 150 mg BD day 0–4
  5. Tablet Olanzapine 5 mg BD D1–4




Skin rash has been reported in patients not pre-treated with a corticosteroid. Standard therapy to reduce the incidence and severity of skin reactions includes dexamethasone 4 mg PO twice daily given the day before, the day of, and the day after pemetrexed administration.

Treatment-related toxicity, including bone marrow suppression, diarrhea, and mucositis, are significantly reduced by supplementing with folic acid and Vitamin B12. Patients should take 0.4 mg oral folic acid (0.35 – 1 mg) daily beginning 1 week before and continuing daily until 3 weeks after the last pemetrexed dose. At least 5 daily doses must be taken during the 7 days before the start of therapy. Patients should also receive Vitamin B12 1000 mcg IM injection 1 week before pemetrexed therapy. This should be repeated every 9 weeks until 3 weeks after the last pemetrexed dose.

Interactions:[2],[3]



Drug-food

No documented interactions

Special instruction for food:

  1. Small frequent meals □
  2. Fruits after washing □
  3. Canned/packed juice □
  4. Hygienic diet




Laboratory monitoring and dose reduction/discontinuation recommendations

Monitoring

Complete blood cell counts, including platelet counts, should be performed on all patients. Patients should be monitored for nadir and recovery, which were tested in the clinical study before each dose and on days 8 and 15 of each cycle. Patients should not begin a new cycle of treatment unless the ANC is ≥1500 cells/mm, the platelet count is ≥100,000 cells/mm3, and creatinine clearance is ≥45 mL/min. Periodic chemistry tests should be performed to evaluate renal and hepatic function.

Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. Treatment may be delayed to allow sufficient time for recovery.



These criteria meet the CTC version 2.0 (NCI 1998) definition of ≥ CTC Grade 2 bleeding.

If patients develop nonhematologic toxicities (excluding neurotoxicity) ≥Grade 3, treatment should be withheld until resolution to less than or equal to the patient's pre-therapy value. Treatment should be resumed according to guidelines in the following Table.

Table: Dose Reduction for Pemetrexed (single-agent or in combination) and Cisplatin - Nonhematologic Toxicities (Excluding neurotoxicity).[2],[3]



In the event of neurotoxicity, the recommended dose adjustments for pemetrexed and cisplatin are as shown in Table.



Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is experienced.

Recommendation for discontinuation

Pemetrexed therapy should be discontinued if a patient experiences any hematologic or nonhematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.

Renally impaired patients

In clinical studies, patients with creatinine clearance ≥45 mL/min required no dose adjustments other than those recommended for all patients. Insufficient numbers of patients with creatinine clearance <45 mL/min have been treated to make dosage recommendations for this group of patients. Therefore, pemetrexed should not be administered to patients whose creatinine clearance is < 45 mL/min using the standard Cockcroft and Gault formula (below) or GFR measured by Tc99m-DPTA serum clearance method:

Caution should be exercised when administering pemetrexed concurrently with NSAIDs to patients whose creatinine clearance is <80 mL/min.


  References Top


  1. Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: The TREAT study. Ann Oncol 2013;24:986-992.
  2. ALIMTA (pemetrexed disodium) Injection. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021462s021lbl.pdf.
  3. Cisplatin Drug Monograph. CCO Formulary; August, 2016. Available at: https://www.cancercareontario.ca/en/drugformulary/drugs/cisplatin.



  Lung - vinorelbine Carboplatin Protocol Top






Oral medication

Cap. Aprepitant 125 mg on day 1 and 80 mg on day 2 and 3.

Cycle is repeated every 3 weeks for a maximum of four cycles.



Side effects: Vinorelbine- carboplatin[1]



Interactions:

  1. Vinorelbine[2],[3]


    1. Acute pulmonary reactions have been reported with vinorelbine and other anticancer vinca alkaloids used in conjunction with mitomycin
    2. Although the pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin, the incidence of granulocytopenia with vinorelbine used in combination with cisplatin is significantly higher than with single-agent vinorelbine
    3. Patients who receive vinorelbine and paclitaxel, either concomitantly or sequentially, should be monitored for signs and symptoms of neuropathy
    4. Administration of vinorelbine to patients with prior or concomitant radiation therapy may result in radiosensitizing effects
    5. Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vinorelbine tartrate with an inhibitor of this metabolic pathway may cause an earlier onset and/or increased severity of side effects.


  2. Carboplatin -


    1. Aminoglycoside antibiotics: increased risk of nephrotoxicity and ototoxicity
    2. Clozapine: increased risk of agranulocytosis, avoid concomitant use
    3. Diuretics: increased risk of nephrotoxicity and ototoxicity
    4. Nephrotoxic drugs: increased nephrotoxicity; not recommended -Phenytoin: reduced absorption of the antiepileptic.


Dose modifications[2],[4]

1. Vinorelbine -

A). Hematological toxicity

Before day 1





Vinorelbine: dosage adjustment not required

  • Hepatic impairment:


Carboplatin: No dose modifications required

Vinorelbine: if patients with hepatic insufficiency are due to metastatic disease, liver function may recover in response to treatment. Therefore, it is suggested that the dose of vinorelbine be reduced to 85% dose and hematological toxicity closely followed up.



  • Neurotoxicity:


Discontinue vinorelbine for NCI CTCAE Grade 3 or higher peripheral neuropathy or autonomic neuropathy causing constipation.




  References Top


  1. Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, et al. Randomized study of vinorelbine – gemcitabine versus vinorelbine – Carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer 2005;49:233-40.
  2. Navelbine Prescrinig information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20388S014lbl.pdf.
  3. Paclitaxel and Carboplatin in NSCLC (Non-Small Cell Lung Cancer). South East London Cancer Network, NHS. Available from: http://www.londoncanceralliance.nhs.uk/media/40047/nsclc_paclitaxel_carbo_protocol_v1.0.pdf
  4. Lung Pathway Group – Carboplatin and IV Vinorelbine in Non-Small Cell Lung Cancer (NSCLC). Available from: http://www.londoncanceralliance.nhs.uk/media/96956/lca-lung-protocol-carboplatin-iv-vinorelbine.pdf.



  Lung - vinorelbine Cisplatin Protocol Top






Oral medication

  • Cap. Aprepitant 125 mg on day 1 and 80 mg on day 2 and 3
  • Tablet Dexamethasone 4 mg BD D2-D4
  • Tablet Ranitidine 150 BD D2-D4
  • Tablet Olanzapine 5 mg BD D1-D4


Cycle is repeated every 3 weeks for a maximum of four cycles.



SIDE effects: vinorelbine- cisplatin[1]



Interactions:[2],[3]

1. Vinorelbine:

  1. Acute pulmonary reactions have been reported with vinorelbine and other anticancer vinca alkaloids used in conjunction with mitomycin
  2. Although the pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin, the incidence of granulocytopenia with vinorelbine used in combination with cisplatin is significantly higher than with single-agent vinorelbine
  3. Patients who receive vinorelbine and paclitaxel, either concomitantly or sequentially, should be monitored for signs and symptoms of neuropathy
  4. Administration of vinorelbine to patients with prior or concomitant radiation therapy may result in radiosensitizing effects
  5. Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vinorelbine tartrate with an inhibitor of this metabolic pathway may cause an earlier onset and/or an increased severity of side effects.




Dose Modifications

Monitoring parameters:

  • CBC with differential and platelet count weekly during treatment
  • Basic metabolic parameter (creatinine and electrolyte) prior to each treatment cycle
  • Liver function tests prior to each treatment cycle
  • Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.





  References Top


  1. Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): A randomised controlled trial. Lancet Oncol 2006;7:719-27.
  2. Vinorelbine Injection. United States Prescribing Information. US National Library of Medicine. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20388S014lbl.pdf.
  3. Cisplatin Drug Monograph, CCO Formulary; August, 2016. Available from: https://www.cancercareontario.ca/en/drugformulary/drugs/cisplatin.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.






 

Top
 
  Search
 
    Similar in PUBMED
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Table of Contents
Lung – pac...
Please Enter Exa...
References
Lung – pac...
Please Enter Exa...
References
Lung – pem...
Please Enter Exa...
References
Lung – pem...
Please Enter Exa...
References
Lung - vinorelbi...
References
Lung - vinorelbi...
References

 Article Access Statistics
    Viewed214    
    Printed48    
    Emailed0    
    PDF Downloaded40    
    Comments [Add]    

Recommend this journal