Large cell carcinoma of the lung medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Overview

Combination chemotherapy regimens using platinum-based chemotherapy and specific-inhibitors is the treatment of choice for the management of patients with large cell carcinoma of the lung. Chemotherapy may be required upon histological subtype of large cell carcinoma of the lung, molecular testing (presence of genetic mutations), and staging. In most cases, the predominant treatment of choice for large cell carcinoma of the lung is neoadjuvant chemotherapy or adjuvant chemotherapy, followed or preceded by surgical resection. There is no consensus on treatment in patients with large cell lung neuroendocrine carcinoma. Commonly used chemotherapeutic agents, include: cisplatin, erlotinib, paclitaxel, docetaxel, carboplatin, etoposide or vinorelbine.

Medical Therapy

  • Initial chemotherapy for patients with large cell carcinoma of the lung will depend on molecular testing, the presence of particular genetic mutations, and staging.
  • Chemotherapy for patients with large cell carcinoma of the lung, is divided into 2 main types:
    • Specific-inhibitor therapy (usually indicated with the presence of a genetic mutation).
    • Platinum-based chemotherapy ( usually indicated with the absence of a genetic mutation).
  • Combination chemotherapy regimens using platinum-based chemotherapy and specific-inhibitors is the treatment of choice for the management of patients with large cell carcinoma of the lung.
  • Erlotinib is the first-line treatment for patients with large cell carcinoma of the lung whose cancer has spread to other parts of the body and that has certain types of epidermal growth factor receptor (EGFR) mutations.
  • Platinum-based chemotherapy (cisplatin, carboplatin, etoposide, irinotecan) are the mainstay of large cell carcinoma of the lung
  • Platinum-based chemotherapy consists of four to six cycles
  • Cisplatin is the preferred platinum based agent of choice when the therapy is used with curative intent
  • Chemotherapy treatments for large cell carcinoma of the lung, include:[1][2][3]

Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy

  • Preferred regimen (1) : Cisplatin 50 mg/m2 days 1 and 8 and vinorelbine 25 mg/m2 days 1, 8, 15, 22, every 28 days for 4 cycles.[4][5][6]
  • Preferred regimen (2) : Cisplatin 100 mg/m2 day 1 and vinorelbine 30 mg/m2 days 1, 8, 15, 22, every 28 days for 4 cycles.
  • Preferred regimen (3) : Cisplatin 75-80 mg/m2 day 1 and vinorelbine 25-30 mg/m2 days 1 + 8, every 21 days for 4 cycles.
  • Preferred regimen (4) : Cisplatin 100 mg/m2 day 1 and etoposide 100 mg/m2 days 1-3, every 28 days for 4 cycles.
  • Preferred regimen (5) : Cisplatin 80 mg/m2 days 1, 22, 43, 64 and vinblastine 4 mg/m2 days 1, 8, 15, 22, 29 then every 2 wks after day 43, every 21 days for 4 cycles.
  • Preferred regimen (6) : Cisplatin 75 mg/m2 day 1 and gemcitabine 1250 mg/m2 days 1, 8, every 21 days for 4 cycles.
  • Preferred regimen (7) : Cisplatin 75 mg/m2 day 1 and docetaxel 75 mg/m2 day 1, every 21 days for 4 cycles.
  • Preferred regimen (8) : Cisplatin 75 mg/m2 day 1 and pemetrexed 500 mg/m2 day 1 for nonsquamous (without specific histologic subtype), every 21 days for 4 cycles.

Chemotherapy Regimens for Patients with Comorbidities or Patients Not Able to Tolerate Cisplatin

Concurrent Chemotherapy and Radiation Therapy Regimens

  • Preferred regimen (1) : Cisplatin 50 mg/m2 on days 1, 8, 29, and 36 and etoposide 50 mg/m2 days 1-5, 29-33 with concurrent thoracic radiation therapy.[8]
  • Preferred regimen (2) : Cisplatin 100 mg/m2 days 1 and 29 and vinblastine 5 mg/m2/weekly x 5 with concurrent thoracic radiation therapy.
  • Preferred regimen (3) : Carboplatin AUC 5 on day 1 and pemetrexed 500 mg/m2 on day 1 every 21 days for 4 cycles with concurrent thoracic radiation therapy.
  • Preferred regimen (4) : Cisplatin 75 mg/m2 on day 1 and pemetrexed 500 mg/m2 on day 1 every 21 days for 3 cycles with concurrent thoracic radiation therapy.

Sequential Chemotherapy and Radiation Therapy Regimens

  • Preferred regimen (1) : Cisplatin 100 mg/m2 on days 1 and 29 and vinblastine 5 mg/m2/weekly on days 1, 8, 15, 22, and 29 followed by radiation therapy.
  • Preferred regimen (2) : Paclitaxel 200 mg/m2 over 3 hours on day 1 and carboplatin AUC 6 over 60 minutes on day 1 every 3 weeks for 2 cycles followed by thoracic radiation therapy.[9]

Concurrent Chemotherapy and Radiation Therapy Followed by Chemotherapy

Complications

References

  1. 1.0 1.1 Alberti, W; Anderson, G; Bartolucci, A; Bell, D; et al. Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomised clinical trials. British Medical Journal, International edition311.7010 (Oct 7, 1995): 899
  2. Ishii K, Ishii N, Shigenobu K, Kasuya Y (1985). "Acetylcholine supersensitivity in the rat heart produced by neonatal sympathectomy". Can. J. Physiol. Pharmacol. 63 (7): 898–9. PMID 4042022. 
  3. Moran T, Sequist L. Timing of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Patients With Lung Cancer With EGFR Mutations. J Clin Oncol 2012; 30:3330
  4. Iyoda A, Makino T, Koezuka S, Otsuka H, Hata Y (June 2014). "Treatment options for patients with large cell neuroendocrine carcinoma of the lung". Gen Thorac Cardiovasc Surg. 62 (6): 351–6. PMC 4042022Freely accessible. PMID 24719260. doi:10.1007/s11748-014-0379-9. 
  5. Lo Russo G, Pusceddu S, Proto C, Macerelli M, Signorelli D, Vitali M, Ganzinelli M, Gallucci R, Zilembo N, Platania M, Buzzoni R, de Braud F, Garassino MC (June 2016). "Treatment of lung large cell neuroendocrine carcinoma". Tumour Biol. 37 (6): 7047–57. PMID 26943800. doi:10.1007/s13277-016-5003-4. 
  6. Battafarano RJ, Fernandez FG, Ritter J, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA (July 2005). "Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer". J. Thorac. Cardiovasc. Surg. 130 (1): 166–72. PMID 15999058. doi:10.1016/j.jtcvs.2005.02.064. 
  7. Fasano M, Della Corte CM, Papaccio F, Ciardiello F, Morgillo F (August 2015). "Pulmonary Large-Cell Neuroendocrine Carcinoma: From Epidemiology to Therapy". J Thorac Oncol. 10 (8): 1133–41. PMC 4503246Freely accessible. PMID 26039012. doi:10.1097/JTO.0000000000000589. 
  8. Derks JL, van Suylen RJ, Thunnissen E, den Bakker MA, Groen HJ, Smit EF, Damhuis RA, van den Broek EC, Speel EM, Dingemans AC (June 2017). "Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?". Eur. Respir. J. 49 (6). PMID 28572122. doi:10.1183/13993003.01838-2016. 
  9. Zappa C, Mousa SA (June 2016). "Non-small cell lung cancer: current treatment and future advances". Transl Lung Cancer Res. 5 (3): 288–300. PMC 4931124Freely accessible. PMID 27413711. doi:10.21037/tlcr.2016.06.07. 
  10. Cicenas S, Zaliene A, Atkocius V (2009). "[Treatment outcome of locally advanced stage IIIA/B lung cancer]". Medicina (Kaunas) (in Lithuanian). 45 (6): 452–9. PMID 19605965. 

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