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]

Stage I

In the tumor central o peripheral?

Peripheral

Central

Is the tumor T1 or T2a?

T1ab, N0

T2a, N0

T1ab-2a, N0

Perform a pretreatment evaluation *If not done, perform pulmonary function tests *Perform bronchoscopy (if possible intraoperative) *Perform a pathological lymph node evaluation *If not done, order PET scan or CT scan

Perform a pretreatment evaluation *If not done, perform pulmonary function tests *Perform bronchoscopy (if possible intraoperative) *Perform a pathological lymph node evaluation *If not done, order PET scan or CT scan

Does the pathological evaluation showed positive disease in the mediastinal lymph nodes?

Does the pathological evaluation showed positive disease in the mediastinal lymph nodes?

Yes

No

Yes

No

Click here for the stage III treatment

Is the tumor operable?

Click here for the stage III treatment

Is the tumor operable?

Yes

No

Yes

No

Surgical resection + lymph node dissection

Radiotherapy with stereotactic ablative radiotherapy

Surgical resection + lymph node dissection

Does the patient presents metastasis to ipsilateral peribronchial and/or hiliar nodesand intrapulmonar nodes (N1)?

Yes

No

Chemotherapy + radiation therapy

Radiotherapy with stereotactic ablative radiotherapy Adjuvant chemotherapy should be added for high-risk stages

Stage II

Has the tumor invaded adjacent structures, such as: chest walls, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium or bronchial tumor smaller than 2 cm?

NO T1a-b, 2a-b, N1 T2b, N0 T3 Tumor larger than 7 cm (not invasive)

Yes IIB: T3 (invasive tumor)

Perform a pretreatment evaluation If not done, perform pulmonary function tests Perform bronchoscopy (if possible intraoperative) Perform a pathological lymph node evaluation If not done, order PET scan or CT scan

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Does the pathological evaluation showed positive disease in the mediastinal lymph nodes?

Yes

No

Click here for the stage III treatment

Is the tumor operable?

Yes

No

Surgical resection + lymph node dissection

Does the patient presents metastasis to ipsilateral peribronchial and/or hiliar nodesand intrapulmonar nodes (N1)?

Yes

No

Chemotherapy + radiation therapy

Radiotherapy with stereotactic ablative radiotherapy Adjuvant chemotherapy should be added for high-risk stages

Metastatic adenocarcinoma

The algorithms for the treatment of metastatic non small cell carcinoma of the lung are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.

Positive sensitizing EGRF mutation

Was the mutation discovered before the initiation of first line therapy?

Yes

No

Initiate erlotinib or afatinib

Suspend or complete chemotherapy and initiate erlotinib or afatinib OR Add erlotinib or afatinib to chemotherapy regimen

Did the tumor progress or respond?

Tumor progression

Positive response or stable tumor

Symptomatic disease

Asymptomatic disease

Systemic metastasis

Brain metastasis

Continue treatment

Multiple metastasis

Single metastasis

Multiple metastasis

Single metastasis

Continue treatment, consider local therapy

Continue treatment, consider whole brain radiation therapy

Continue treatment, consider local therapy

Consider platinum doublet with or without Bevacizumab AND/OR Erlotinib

Positive ALK mutation

Was the mutation discovered before the initiation of first line therapy?

Yes

No

Initiate crizotinib

Suspend or complete chemotherapy and initiate crizotinib

Did the tumor progress or respond?

Tumor progression

Positive response or stable tumor

Symptomatic disease

Asymptomatic disease

Systemic metastasis

Brain metastasis

Continue treatment or change to certinib according to the degree of disease

Multiple metastasis

Single metastasis

Multiple metastasis

Single metastasis

Continue treatment, consider local therapy

Continue treatment, consider whole brain radiation therapy

Continue treatment, consider local therapy

Initiate certinib OR Consider platinum doublet with or without Bevacizumab AND/OR Erlotinib

Negative EGRF and ALK or unknown mutation

What is the performance status (PS) of the patient?

0-1

2

3-4

Doublet chemotherapy OR Bevacizumab + Chemotherapy OR Cetuximab/vinorelbine/cisplatin

Chemotherapy

Supportive care

What was the tumor response to the treatment?

Progression

Positive response or stable tumor

Administer 4-6 cycles and assess progression of the disease

PS 0-2

PS 3-4

Tumor progression

Positive response or stable tumor

Initiate docetaxel or pemetrexed or erlotinib or gemcitabine

Provide supportive care

Initiate docetaxel or pemetrexed or erlotinib or gemcitabine

Continuation maintenance (cetuximab or gemcitabine) OR Switch maintenance (erlotinib or decetaxel) OR Close observation

Initiate docetaxel or pemetrexed or erlotinib or gemcitabine

Metastatic squamous cell carcinoma

What is the performance status (PS) of the patient?

0-1

2

3-4

Doublet chemotherapy OR Cetuximab/vinorelbine/cisplatin

Chemotherapy

Suportive care

What was the tumor response to the treatment?

Progression

Positive response or stable tumor

Administer 4-6 cycles and assess progression of the disease

PS 0-2

PS 3-4

Tumor progression

Positive response or stable tumor

Initiate docetaxel or erlotinib or gemcitabine

Provide suportive care

Initiate docetaxel or erlotinib or gemcitabine

Continuation mantainance (cetuximab or gemcitabine) OR Switch mantainance (erlotinib or decetaxel) OR Close observation

Initiate docetaxel or erlotinib or gemcitabine

Chemotherapeutic regimens

The table below is based on 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: patients with comorbidities or can't tolerate cisplatin

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

Chemotherapy plus radiotherapy regimens

Regimens are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines; Chemotherapy regimens used with radiation therapy section.

Chemotherapy plus radiotherapy

• 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 radiotherapy
• Cisplatin 100 mg/m² on days 1 and 29 + vinblastin 5 mg/m² weekly for 5 weeks + thoracic radiotherapy
• 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 radiotherapy
• 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 radiotherapy

References

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