Non small cell lung cancer medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2] Maria Fernanda Villarreal, M.D. [3]

Overview

Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The predominant therapy for non-small cell lung cancer is surgical resection. Chemotherapy and chemo-radiation may be required upon histological subtype of non-small cell lung cancer, location, size, and lymph node involvement. Commonly used chemotherapeutic agents include gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide or vinorelbine.

Medical Therapy

Initial medical therapy for patients with non-small cell lung cancer will depend on tumor histology and molecular testing (presence of genetic mutations).

• If the tumor demonstrates the absence of genetic mutation or is a squamous-cell tumor, the treatment of choice will be platinum-based chemotherapy.
• If the tumor is a non-squamous cell tumor and positive for molecular testing, the treatment of choice will be with a specific-inhibitor such as:

• EGFR mutation (erlotinib, gefitinib, afatinib)
• ALK mutation (crizotinib)
• ROS1 mutation (crizotinib)

• Targeted therapy agents include erlotinib, crizotinib, gefitinib,afatinib, and denosumab
• Targeted agents usually inhibit tyrosine kinase at the epidermal growth factor receptor
• Chemotherapy is indicated as adjuvant for stage IB, II, and III non-small cell lung cancer
• Platinum-based chemotherapy (cisplatin, carboplatin, etoposide, irinotecan) are the mainstay of treatment for non-small cell lung cancer
• Platinum-based chemotherapy consists of four to six cycles
• In patients with non-squamous histology, platinum-based chemotherapy may be supplemented by bevacizumab
• Other chemotherapy regimens may be an alternative for non-small cell lung cancer patients who are unable to tolerate a platinum-based chemotherapy. These include:
  • Cyclophosphamide
  • Doxorubicin (adriamycin)
  • Vincristine
• For non-small cell lung cancer patients with good treatment response and with stable disease after initial chemotherapy, maintenance therapy may prolong survival

Chemotherapeutic Regimens

Shown below is a table depicting the different choices of regimens for the initial or adjuvant chemotherapy of patients with non-small cell lung cancer. The list of regimens has been adapted from the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

Cisplatin Based Therapy

Agent	Recommended regimen
Cisplatin 50 mg/m2 + vinorelbine 25 mg/m2	Cisplatin on days 1 and 8, vinorelbine on days 1, 8, 15, 22 and every 28 days to a total of 4 cycles
Cisplatin 100 mg/m2 + vinorelbine 30 mg/m2	Cisplatin on day 1, vinorelbine on days 1, 8, 15, 22 and every 28 days to a total of 4 cycles
Cisplatin 75-80 mg/m2 + vinorelbine 25-50 mg/m2	Cisplatin on day 1, vinorelbine on days 1, 8 and every 21 days to a total of 4 cycles
Cisplatin 80 mg/m2 + vinorelbine 4 mg/m2	Cisplatin on days 1, 22, 43, 64, then every 21 days to a total of 4 cycles, vinorelbine on days 1, 8, 15, 22, 29, every 2 weeks after day 43 until the completion of cisplatin treatmet
Cisplatin 100 mg/m2 + etoposide 100 mg/m2	Cisplatin on day 1, etoposide through days 1 to 3 and every 28 days to a total of 4 cycles
Cisplatin 75 mg/m2 + gemcitabine 1250 mg/m2	Cisplatin on day 1, gemcitabine on days 1, 8 and every 21 days to a total of 4 cycles
Cisplatin 75 mg/m2 + docetaxel 75 mg/m2	Cisplatin on day 1, docetaxel on day 1 and every 21 days to a total of 4 cycles
Cisplatin 50 mg/m2 + pemetrexed 500 mg/m2	Cisplatin on day 1, pemetrexed on days 1 and every 21 days to a total of 4 cycles

Alternative Regimen

Paclitaxel 200 mg/m² on day 1 + carboplatin area under the concentration (AUC) 6 on day 1 and then every 21 days.

Chemotherapy with Radiation Therapy Regimens

Chemotherapy plus Radiation Therapy

The list bellow show the options for concomitant chemotherapy plus radiation therapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

• Cisplatin 50 mg/m² on days 1, 8, 29 and 36 + etoposide 50 mg/m² through days 1 to 5 and then 29 to 33 + thoracic radiation therapy
• Cisplatin 100 mg/m² on days 1 and 29 + vinblastine 5 mg/m² weekly for 5 weeks + thoracic radiation therapy
• Cisplatin 75 mg/m² on the first day + pemetrexed 500 mg/m² on day 1 and then every 21 days to a total of 3 cycles + thoracic radiation therapy
• Carboplatin AUC 5 on the first day + pemetrexed 500 mg/m² on day 1 and then every 21 days to a total of 3 cycles + thoracic radiation therapy

Chemotherapy Followed by Radiation Therapy

The list bellow show the options for chemotherapy followed by radiation therapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

• Cisplatin 100 mg/m² on days 1 and 29 + vinblastine 5 mg/m² per week on days 1, 8, 15, 22 and 29 followed by thoracic radiation therapy.
• Paclitaxel 200 mg/m² administered for 3 hours in the first day + carboplatin AUC 6 administered in 1 hour and then every 21 days to a total of 2 cycles followed by thoracic radiation therapy.

Chemotherapy plus Radiation Therapy, Followed by Chemotherapy

The list bellow show the options for concomitant chemotherapy plus radiation therapy followed by chemotherapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

• Cisplatin 50 mg/m² on days 1, 8, 29 and 36 + etoposide 50 mg/m² through day 1 to 5 and then 29 to 33 + thoracic radiation therapy, then followed by cisplatin 50 mg/m² + etoposide 50 mg/m² to a total of 2 cycles.
• Paclitaxel 45 to 50 mg/m² once a week + carboplatin AUC 2 + thoracic radiation therapy, then followed by Paclitaxel 200 mg/m² + carboplatin AUC 6 to a total of 2 cycles.

Complications

Medical therapy complications for non-small cell lung cancer will depend on the chemotherapeutic agent.

• Common chemotherapy complications for platinum-based chemotherapy include:
  • Neurotoxicity
  • Peripheral neuropathies
• Other chemotherapeutic agent complications include:
  • Extravasation
  • Cardiotoxicity

References

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