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] Trusha Tank, M.D.[4]

## Overview

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Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The main 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. Chemotherapeutic regimens are based on platinum agents such as cisplatin, carboplatin, oxaliplatin, and satraplatin. Alternative regimens include paclitaxel, gemcitabine, or etoposide. Chemotherapeutic regimens are adjusted based on individual characteristics and body surface. The regimen adjustment according to tumor evolution has demonstrated longer survival rates, optimal symptom control, and higher quality of life. Radiation therapy can be applied to any stage of non-small cell lung cancer. In general, radiation therapy is recommended as palliative care treatment among patients who develop an advanced stage of non-small cell lung cancer or symptomatic patients with local involvement (pain, vocal cord paralysis, and hemoptysis). Curative radiation therapy may be indicated in patients who are not suitable for surgery with early-stage non-small cell lung cancer. The main goal of radiation therapy for non-small cell lung cancer is maximum tumor control with minimal tissue toxicity. The two main types of radiation therapy for non-small cell lung cancer are external beam radiation therapy (thoracic radiotherapy), and brachytherapy (internal radiation therapy).

## Medical Therapy

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Initial medical therapy for patients with non-small cell lung cancer will depend on tumor histology and molecular testing (presence of genetic mutations).[1]

* 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

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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 2019 NCCN Non-Small Cell Lung Cancer guidelines.[2][3][4]

### Cisplatin Based Therapy

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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

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Paclitaxel 200 mg/m2 on day 1 + carboplatin area under the concentration (AUC) 6 on day 1 and then every 21 days.[3]

## Chemotherapy with Radiation Therapy Regimens

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### Chemotherapy plus Radiation Therapy

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The list below show the options for concomitant chemotherapy plus radiation therapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[3]

* 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

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The list below show the options for chemotherapy followed by radiation therapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[3]

* 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

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The list below show the options for concomitant chemotherapy plus radiation therapy followed by chemotherapy based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[3]

* 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

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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

### Radiation Therapy Regimens

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Shown below is a list of the different regimens radiation therapy for patients with non-small cell lung cancer. The list of regimens has been adapted from the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[5][3]

#### Usual Dosages for Definitive Radiation Therapy

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Administer fractions of 2 Gy over a period of 6 to 7.5 weeks to a total dose of 60 to 74 Gy

#### Neoadjuvant Radiation Therapy Regimen

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Administer fractions of 1.8 to 2 Gy over a period of 5 weeks to a total dose of 45 to 50 Gy

#### Adjuvant Radiation Therapy Regimens

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* Negative surgical piece margins: Administer fractions of 1.8 to 2 Gy over a period of 5 to 6 weeks to a total dose of 40 to 54 Gy
* Positive surgical piece margins: Administer fractions of 1.8 to 2 Gy over a period of 6 weeks to a total dose of 54 to 60 Gy
* Extracapsular nodal extension: Administer fractions of 1.8 to 2 Gy over a period of 6 weeks to a total dose of 60 to 70 Gy
* Residual tumor: Administer fractions of 2 Gy over a period of 6 to 7 weeks to a total dose of 54 to 60 Gy

#### Stereotactic Ablative Radiotherapy Usual Dosage

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* Peripheral small tumors: 25 to 34 Gy not fractioned.
* Peripheral tumors and chest wall tumors larger than 1 cm: 45 to 60 Gy administered in 3 fractions
* Central or peripheral tumors smaller than 5 cm: 48 to 60 Gy administered in 4 fractions
* Central or peripheral tumors principally chest wall tumors smaller than 1 cm: 50 to 55 Gy administered in 5 fractions
* Central tumors: 60 to 70 Gy administered in 8 to 10 fractions

## Palliative Radiation Therapy Regimens

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Listed below are the recommended palliative radiation therapy regimens for patients with non-small cell lung cancer according to the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[3]

* Obstructive disease
* Administer fractions of 3 Gy over a period of 2 to 3 weeks to a total dose of 30 to 45 Gy
* Bone metastases associated with the soft tissue mass
* Administer fractions of 4 to 3 Gy over a period of 1 to 2 weeks to a total dose of 20 to 30 Gy
* Bone metastases not associated with the soft tissue mass
* Administer fractions of 8 to 3 Gy over a period of 1 to 14 days to a total dose of 8 to 30 Gy
* Patients with poor performance status and symptomatic chest disease
* Administer fractions of 8.5 Gy over a period of 7 to 14 days to a total dose of 17 Gy
* Metastatic disease in patients who have a poor performance status
* Administer fractions of 8 to 4 Gy over a period of 1 to 7 days to a total dose of 8 to 20 Gy
* Whole brain radiation therapy regimens for metastases to the brain, include the following:
* 10 fractions of 3 Gy each to a total of 30 Gy
* 15 fractions of 2.5 Gy each to a total of 37.5 Gy
* 5 fractions of 4 Gy each to a total of 20 Gy (Good option for patients with poor performance status)

## References

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1. ↑ D'Antonio; Passaro A; Gori B (May 2014). "Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies". Therapeutic Advances in Medical Oncology. 6 (3): 101–114. doi:10.1177/1758834014521110. PMC 3987652. PMID 24790650.
2. ↑ 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 randomized clinical trials. British Medical Journal, International edition311.7010 (Oct 7, 1995): 899
3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 https://www.nccn.org/professionals/physician_gls/recently_updated.aspx
4. ↑ "Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group". BMJ. 311 (7010): 899–909. October 1995. PMC 2550915. PMID 7580546.
5. ↑ Pattern of use of radiotherapy for lung cancer: a descriptive study. BioMed Central. http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-697#CR6 Accessed on March 1, 2016

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