Treatment algorithm

Your Organizational Guidance

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Kleincellige en niet-kleincellige longkanker: diagnose, behandeling en opvolgingPublished by: KCELast published: 2013Cancer du poumon à petites cellules et non à petites cellules : diagnostic, traitement et suiviPublished by: KCELast published: 2013

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

at initial presentation: limited disease

1st line – chemotherapy

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ACUTE
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at initial presentation: limited disease
1st line – 

chemotherapy

Care of patients with small cell lung cancer (SCLC) should be undertaken by a multidisciplinary team in a specialized oncology center.

Patients with limited-stage SCLC are treated with concurrent chemotherapy and radiation therapy (RT).[52][53]​ Chemotherapy typically consists of cisplatin and etoposide, although carboplatin is frequently substituted for cisplatin.[5][31]​​​​

All chemotherapy agents have the potential to cause bone marrow suppression, nausea/vomiting, alopecia, and fatigue. Other adverse effects are specific to the particular agent.

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

and

etoposide

Secondary options

carboplatin

and

etoposide

Plus – radiation therapy

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ACUTE
|
at initial presentation: limited disease
Plus – 

radiation therapy

Treatment recommended for ALL patients in selected patient group

Radiation therapy (RT) is standard in patients with limited-stage SCLC. Early RT (given with cycle 1 or 2 of chemotherapy) is preferred to RT administered later in the chemotherapy course.[53][54]

Twice-daily radiation dosing (45 Gy in 1.5-Gy fractions) is preferred though once-daily dosing (approximately 60-70 Gy in 2-Gy fractions) is acceptable if twice-daily dosing is not feasible.[55][56][57]​​​ 

Adverse effects depend on the size of the radiation field, the dose, and the adjacent organs (the lungs and esophagus, in particular), which unavoidably receive some radiation.

The most common adverse effects are fatigue, skin erythema/desquamation, and esophagitis. Most patients develop some degree of esophagitis during treatment. The most common late complication is pneumonitis, which is characterized by dyspnea, dry cough, and fever occurring 1 to 6 months after completing treatment. Pneumonitis is rarely fatal. Most patients develop some degree of lung fibrosis after RT, but this is usually asymptomatic.

Rare complications include esophageal stricture and bronchial stenosis, which are more common when higher doses of radiation are prescribed.[33][76][77]

Plus – prophylactic cranial irradiation

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ACUTE
|
at initial presentation: limited disease
Plus – 

prophylactic cranial irradiation

Treatment recommended for ALL patients in selected patient group

Patients with SCLC are at high risk of developing brain metastases. Randomized trials have demonstrated a survival benefit for prophylactic cranial irradiation (PCI) in patients who respond to initial therapy. The data are stronger in limited-stage disease than in extensive-stage disease.[50][53][70]

Among patients receiving PCI, the recommended dose is 25 Gy in 2.5-Gy fractions.[72][73]

Consider – durvalumab (consolidation therapy)

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ACUTE
|
at initial presentation: limited disease
Consider – 

durvalumab (consolidation therapy)

Treatment recommended for SOME patients in selected patient group

Durvalumab, an anti-programmed cell death 1 ligand (PD-L1) monoclonal antibody, is recommended as consolidation therapy for up to 2 years for patients with limited-stage small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.[5][58][59]

Prophylactic cranial irradiation, if considered, should be administered before durvalumab consolidation therapy.[5]

See local specialist protocol for dosing guidelines.

Primary options

durvalumab

Consider – surgery

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ACUTE
|
at initial presentation: limited disease
Consider – 

surgery

Treatment recommended for SOME patients in selected patient group

Surgical intervention has limited use in SCLC because most patients present with advanced disease. For the rare patient with a solitary pulmonary mass without radiographic evidence of lymphadenopathy, it is recommended that preoperative mediastinoscopy be performed to confirm N0 status. For these patients, surgical resection, typically a lobectomy, is reasonable. Postoperative chemotherapy should then be administered. Patients with resected limited-stage SCLC with N2 status should receive mediastinal radiation in addition to chemotherapy; postoperative radiation may be considered in patients with N1 status.​[5][31][60]​​​

Lobectomy involves division of the lobar pulmonary arteries, pulmonary veins, the associated bronchus, hilar lymph nodes, and removal en bloc. Access to the chest is usually via a thoracotomy, although minimally invasive techniques (i.e., video-assisted thoracoscopic surgery) are gaining favor due to shorter hospitalizations and less postoperative pain. Sampling or dissection of mediastinal lymph nodes is recommended.

US guidelines recommend preoperative exercise for people undergoing surgery for lung cancer, as it can lead to a shorter hospital stay and reduced risk of postoperative complications.[61]​ Aerobic and resistance exercise during treatment with curative intent is recommended to reduce the adverse effects of treatment.[61]​​

See Non-small cell lung cancer for further surgical details.

at initial presentation: extensive disease

1st line – chemotherapy ± immunotherapy

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ACUTE
|
at initial presentation: extensive disease
1st line – 

chemotherapy ± immunotherapy

Patients with extensive-stage small cell lung cancer (ES-SCLC) typically receive chemotherapy plus immunotherapy for 4 to 6 cycles followed by maintenance immunotherapy until disease progression or unacceptable toxicities.[5][31]​​[62][63]​​​​​​​ Commonly used regimens include cisplatin plus etoposide plus durvalumab, or carboplatin plus etoposide plus either atezolizumab or durvalumab. Atezolizumab/hyaluronidase (a subcutaneous formulation of atezolizumab) may be substituted for atezolizumab.[5]​ Atezolizumab or durvalumab can be omitted if there are contraindications to immune checkpoint inhibitors. Cisplatin or carboplatin plus irinotecan is an additional option.[5][31]

Atezolizumab and durvalumab can cause unique immune-mediated adverse events that are not seen with traditional cytotoxic chemotherapy, such as pneumonitis, colitis, dermatitis, myositis, and hypothyroidism, among others. Awareness of the array of possible immune-mediated adverse events by both provider and patient is critical for early recognition and mitigation of potential drug to drug interactions.[64][65]​ Immune checkpoint inhibitors should not be used in patients who are currently taking or have previously received tyrosine kinase inhibitors (TKIs); toxicity has been reported with both concurrent and sequential administration of immunotherapy and TKI in nonsmall cell lung cancer trials.[5][66]

All chemotherapeutic treatments have the potential to cause bone marrow suppression, nausea/vomiting, alopecia, and fatigue. Other adverse effects are specific to the particular agent. See local specialist protocol for dosing guidelines.

Primary options

carboplatin

-- AND --

etoposide

-- AND --

atezolizumab

or

atezolizumab/hyaluronidase

or

durvalumab

OR

cisplatin

and

etoposide

and

durvalumab

OR

cisplatin

or

carboplatin

-- AND --

irinotecan

OR

cisplatin

or

carboplatin

-- AND --

etoposide

Plus – prophylactic cranial irradiation or routine surveillance with MRI brain

Back
ACUTE
|
at initial presentation: extensive disease
Plus – 

prophylactic cranial irradiation or routine surveillance with MRI brain

Treatment recommended for ALL patients in selected patient group

Patients with SCLC are at high risk of developing brain metastases. Randomized trials have demonstrated a survival benefit for prophylactic cranial irradiation (PCI) in patients who respond to initial therapy. The data are stronger in limited-stage disease than in extensive-stage disease.[50][53][70]

Among patients receiving PCI, the recommended dose is 25 Gy in 2.5-Gy fractions.[72][73]

Depending on patient- and disease-specific characteristics, routine surveillance with a magnetic resonance imaging (MRI) scan of the brain may be an alternative to PCI.[53]

Consider – radiation therapy

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ACUTE
|
at initial presentation: extensive disease
Consider – 

radiation therapy

Treatment recommended for SOME patients in selected patient group

Radiation therapy (RT) is effective in palliating symptoms of advanced intrathoracic disease (i.e., hemoptysis, chest pain, shortness of breath) as well as symptomatic metastatic sites (e.g., bone and brain metastases).

Patients with limited sites of metastatic disease who achieve a complete extrathoracic response and at least a partial intrathoracic response to initial chemotherapy can be considered for thoracic RT to delay or prevent recurrent symptomatic disease.[53][68][69]

Adverse effects depend on the size of the radiation field, the dose, and the adjacent organs (the lungs and esophagus, in particular), which unavoidably receive some radiation.

The most common adverse effects are fatigue, skin erythema/desquamation, and esophagitis. Most patients develop some degree of esophagitis during treatment. The most common late complication is pneumonitis, which is characterized by dyspnea, dry cough, and fever occurring 1 to 6 months after completing treatment. Pneumonitis is rarely fatal. Most patients develop some degree of lung fibrosis after RT, but this is usually asymptomatic.

Rare complications include esophageal stricture and bronchial stenosis, which are more common when higher doses of radiation are prescribed.[33][76][77]

ONGOING

relapse within 6 months

1st line – systemic therapy or radiation therapy

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ONGOING
|
relapse within 6 months
1st line – 

systemic therapy or radiation therapy

There are numerous chemotherapy drugs and combinations that may be used if a clinical trial is not feasible, although response rates for relapsed small cell lung cancer (SCLC) are low. Time to relapse can, however, help to inform treatment decisions for patients with relapsed SCLC.[5]

Consideration may be given to the original, or a similar, platinum-based regimen for patients with early relapse (treatment-free interval of at least 3 to 6 months).[5][31]​ Other suitable options are discussed in guidelines.[5]

Tarlatamab, a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, is recommended as a subsequent treatment option for patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.[5][59][78]

Single-agent nivolumab or pembrolizumab are listed as subsequent treatment options for patients with relapsed SCLC with treatment-free interval ≤6 months.[5][31]​ Nivolumab/hyaluronidase (a subcutaneous formulation of nivolumab) may be substituted for nivolumab.[5]​ Nivolumab, however, did not improve survival versus chemotherapy in a randomized open-label phase 3 trial of relapsed SCLC.[75]​ The use of nivolumab or pembrolizumab in patients with disease progression while receiving maintenance atezolizumab or durvalumab is discouraged.[5]

The response of patients with resistant or refractory disease (treatment-free interval <3 months or ≤6 months for European and US guidance, respectively) to subsequent therapies is poor and a clinical trial may be the preferred option.[5][31]

For patients with symptomatic intrathoracic disease or with distant metastases causing distressing symptoms, palliative radiation therapy should be considered.

All chemotherapeutic treatments have the potential to cause bone marrow suppression, nausea/vomiting, alopecia, and fatigue. Other adverse effects are specific to the particular agent.

Immune checkpoint inhibitors can cause pneumonitis, colitis, dermatitis, myositis, and hypothyroidism, among others. Awareness of the array of possible immune-mediated adverse events by both provider and patient is critical for early recognition and mitigation of drug to drug interactions.[64][65]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

or

carboplatin

-- AND --

etoposide

OR

cisplatin

or

carboplatin

-- AND --

irinotecan

Secondary options

topotecan

OR

lurbinectedin

OR

paclitaxel

OR

docetaxel

OR

temozolomide

OR

etoposide

OR

irinotecan

OR

tarlatamab

OR

gemcitabine

OR

cyclophosphamide

and

doxorubicin

and

vincristine

Tertiary options

nivolumab

OR

nivolumab/hyaluronidase

OR

pembrolizumab

relapse after 6 months

1st line – systemic therapy or radiation therapy

Back
ONGOING
|
relapse after 6 months
1st line – 

systemic therapy or radiation therapy

There are numerous chemotherapy drugs and combinations that may be used if a clinical trial is not feasible, although response rates for relapsed small cell lung cancer (SCLC) are low. Time to relapse can, however, help to inform treatment decisions for patients with relapsed SCLC.[5]

US guidelines recommend the original or a similar platinum-based regimen as subsequent systemic therapy for patients with treatment-free interval >6 months.[5]

One meta-analysis of observational and randomized study data found that platinum-doublet chemotherapy was associated with a significantly higher objective response rate and disease control rate in patients with relapsed SCLC compared with non-platinum-based regimens.[74]​ Other suitable options are discussed in guidelines.[5]

Tarlatamab, a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, is recommended as a subsequent treatment option for patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.[5][59][78]

For patients with symptomatic intrathoracic disease or with distant metastases causing distressing symptoms, palliative radiation therapy should be considered.

All chemotherapeutic treatments have the potential to cause bone marrow suppression, nausea/vomiting, alopecia, and fatigue. Other adverse effects are specific to the particular agent.

Immune checkpoint inhibitors can cause pneumonitis, colitis, dermatitis, myositis, and hypothyroidism, among others. Awareness of the array of possible immune-mediated adverse events by both provider and patient is critical for early recognition and mitigation of drug to drug interactions.[64][65]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

or

carboplatin

-- AND --

etoposide

OR

cisplatin

or

carboplatin

-- AND --

irinotecan

Secondary options

lurbinectedin

OR

tarlatamab

OR

topotecan

OR

irinotecan

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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