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Chemotherapy for small cell lung cancer


Medical editor Odd Terje Brustugun MD
Oncologist

Oslo University Hospital
Norway

General

Chemotherapy is used in combination with radiation treatment for limited disease small cell lung cancer (SCLC-LD), and alone for extensive disease small cell lung cancer (SCLC-ED). Response is expected in about 90% and 50% of the patients, respectively. Ten to 15% of patients with localized cancer and 1-2% of patients with extensive cancer will live for more than 5 years.

In patients with T1-2N0-1 disease, surgical treatment may be appropriate. It is assumed that up to 10% of patients with localized cancer may be candidates for a successful resection. Postoperative chemotherapy is required since small cell lung cancer are at high-risk to metastasize, also in early stage.

First choice chemotherapy for localized cancer, and in younger patients (< 75 years) with extensive cancer, is platinum and etoposide. Cistplatin seems superior to carboplatin combined with radiation treatment. In extensive disease, carboplatin might be chosen due to less toxicity and ease of administration.  

Recurrence treatment

About 80% of patients with limited cancer and virtually all with extensive cancer will have recurrence of the disease. A few phase II-studies have been presented in the second line setting of SCLC. Topoisomerase inhibitors (irinotecan/topotecan) and the triple-combination with cyclophosphamide, vincristin and doxorubicin has shown activity and might be used. The expected treatment benefit must be weighed against the patient's general health status and expected survival time. For relapse three months or more after ended first line treatment, it may be appropriate to try the same regimen again. For early recurrence, another chemotherapy regimen should be considered. Radiation therapy will often provide successful symptom relief and may be considered instead of chemotherapy.

Chemotherapy for reduced general health condition and elderly patients with small cell lung cancer

Even patients with reduced general health status due to localized cancer, can achieve significant benefit from treatment. The goal is curative also for these patients. If the reduced status of the patient is due to another illness, the treatment chosen should have few side effects.

For extensive cancer, the threshold for treatment should be higher, especially in older patients or patients with reduce general health status. It should be considered whether active treatment should be given at all.  

Indication

  • Small cell lung cancer

Goal

  • For localized cancer, the treatment is intended to cure the disease.
  • For extensive cancer, the treatment is primarily palliative. 

Treatment Plan

The treatment plan for patients with small cell lung cancer is available in an interactive flow chart. This is a feature to provide an overview of treatment for the different patient groups.

Click here to open the flow chart

Small cell cancer – Limited disease

Many chemotherapy drugs have been tried for small cell lung cancer, but platinum-based regimens have proven to be more effective than other regimens such as anthracycline combinations. In Norway, as in most other countries, a combination of cisplatin and etoposide (PV regimen) is most commonly used. Carboplatin can be used instead of cisplatin (CV regimen), but has somewhat less documentation. The latter is easier to manage because the patient does not require hydration during the treatment. Treatment beyond 6 courses has not been shown to be of any benefit.

Chemotherapy in combination with radiation for limited disease

For localized cancer, a combination treatment with PV-regimen and radiation therapy has shown a synergistic effect and prolongs survival compared to chemotherapy or radiation alone. Only platinum-based regimens have this documentation. Four courses of chemotherapy are usually administered with radiation starting after 2 or 3 chemotherapy cycles (alternating with radiation therapy). Concomitant treatment (simultaneous treatment) has the greatest effect but also the most side effects such as esophagitis and hematological toxicity. For patients in reduced general health status, it is therefore advantageous to start the next course of chemotherapy after the radiation treatment is completed. For a more agressive treatment, chemotherapy is administered every 3 weeks regardless of ongoing radiation treatment.

Small cell cancer – Extensive disease

For extensive cancer, treatment is palliative and is usually not combined with radiation treatment. Platinum-based treatments are also first choice treatment due to the greater effect than anthracycline-based treatments and can be expected to give an objective response in 50-80% of patients. The median survival time increases from 2 to 10 months, and symptom control and life quality improves. Unfortunately, complete remissions are rare and the response duration is short.

PV courses are appropriate as for limited disease, but CV courses are considered equally effective and are often chosen due to fewer side effects.  

For ages over 75 years or reduced general health status, ACO treatments are a good choice due to sparse side effects.


Preparation

The patient is thoroughly informed verbally and in writing about the goal of the treatment, how it will be carried out, what side effects can be expected, and what is expected of the patient during the treatment period. 

During treatment of lung cancer with chemotherapy, neutropenia is the most common cause of dose reduction. Blood tests must therefore always be performed before starting a new course of treatment. 

For cisplatin-containing chemotherapy regimens, kidney function must also be checked. 

The patient will be offered a customized wig.


Implementation

PV regimen (cisplatin and etoposide)

Four treatment courses are usually given.

  • Day 1: cisplatin and etoposide intravenously.
  • Day 2 and 3: etoposide intravenously or day 2-4 etoposide orally.
  • Day 22: start of new treatment course.

CV regimen (carboplatin and etoposide)

Four treatment courses are given. The carboplatin dose is calclulated according to the Calvert formula.

  • Day 1: carboplatin and etoposide intravenously.
  • Day 2 and 3: etoposide intravenously or day 2-4 etoposide orally. 
  • Day 22: start new treatment course.

ACO regimen (doxorubicin, cyclophosphamide and vincristine)

Four treatment courses are given.

  • Day 1: doxorubicin, vincristine, and cyclophosphamide intravenously.
  • Day 22: start new treatment course.

Dose reduction

Dose reduction for low blood values
Leukocytes or Thrombocytes Chemotherapy dose
³ 3.0 ³ 100 100 %
2.5–2.9 75–99  75 %
2.0–2.4 50–74  50 %
< 2.0 < 50 Postpone treatment 1 week


Follow-up

The treatment effect is most often evaluated in 2-3 month intervals. The first check should take place 4-8 weeks after treatment is completed.

Evaluation often includes chest X-ray or CT.

If there is objective, good, or complete objective response after the first treatment, both for localized and extensive cancer, the patient should be referred for radiation therapy of the brain to prevent brain metastasis. 

 

Some chemotherapy side effects for small cell lung cancer (1)

(Frequent > 1/100, rare < 1/1000)

Side Effect  Cisplatin Etoposide  Carboplatin Doxorubicin Vincristine Cyclophosphamide
Bone marrow depression Frequent Frequent Frequent Frequent Frequent Frequent
Nausea/Vomiting   High Mild Moderate Moderate Minimal High/
moderate
Hair loss Rare Frequent Frequent Frequent Frequent In high doses
Diarrhea/
Constipation
Diarrhea/
Frequent
Frequent Frequent Diarrhea/
Rare
Constipation/
frequent
Dose-dependent
Mucositis/
Stomatitis
Not reported Frequent Not reported Stomatitis/
Rare
Stomatitis/
Frequent
Dose-dependent
Allergic reactions Rare Rare Frequent Rare Rare Frequent
Cardiotoxicity Rare Not reported Frequent Frequent Rare Rare
Neurological symptoms Frequent Rare Frequent Not reported Frequent Not reported
Skin/nails Rare Not reported Frequent Frequent Not reported Rare
Liver Frequent Rare Frequent Not reported Not reported Frequent
Airways Not reported Rare Not reported Not reported Not reported Rare

With use of cisplatin, about 30% of the patients experience ototoxic side effects.

PV regimen = cisplatin and etoposide

CV regimen = carboplatin and etoposide

ACO regimen = doxorubicin, cyclophosphamide, and vincristine 


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