Lung cancer

Extensive Stage Small Cell Lung Cancer

As in limited stage small cell carcinoma, chemotherapy should be given as multiple agents in doses associated with at least moderate toxic effects in order to produce the best results in extensive stage disease. Doses and schedules used in current programs yield overall response rates of 70% to 85% and complete response rates of 20% to 30% in extensive stage disease. Since overt disseminated disease is present, combination chemotherapy is the cornerstone of treatment of this stage of small cell lung cancer. Combinations containing two or more drugs are needed for maximal benefit.

The relative effectiveness of many 2- to 4-drug combination programs appears similar, and there are a large number of potential combinations. Therefore, a representative selection of regimens that have been found to be effective by at least two independent groups has been provided. Some physicians have administered two of these or other regimens in alternating sequences, but there is no proof that this strategy yields substantial survival improvement. Optimal duration of chemotherapy is not clearly defined, but there is no obvious improvement in survival when the duration of drug administration exceeds 6 months. There is no clear evidence from reported data that maintenance chemotherapy will improve survival duration.

Combination chemotherapy plus chest irradiation does not appear to improve survival compared with chemotherapy alone in extensive stage small cell lung cancer. However, radiation therapy plays an extremely important role in palliation of symptoms of the primary tumor and of metastatic disease, particularly brain, epidural, and bone metastases.

Chest irradiation is sometimes given for superior vena cava syndrome, but chemotherapy alone (with irradiation reserved for nonresponding patients) is appropriate initial treatment. Brain metastases are appropriately treated with whole-brain radiation therapy. However, intracranial metastases from small cell carcinoma may respond to chemotherapy as readily as metastases in other organs.

Patients with small cell lung cancer treated with chemotherapy with or without chest irradiation who have achieved a complete remission can be considered for administration of prophylactic cranial irradiation (PCI).

Many more patients with extensive stage small cell carcinoma have greatly impaired performance status at the time of diagnosis when compared to patients with limited stage disease. Such patients have a poor prognosis and tolerate aggressive chemotherapy or combined modality therapy poorly. Single-agent intravenous, oral, and low-dose biweekly regimens have been developed for these patients. However, prospective randomized studies have shown that patients with a poor prognosis who are treated with conventional regimens live longer than those treated with the single-agent or low-dose regimens.

Treatment options:

Standard:

1. Combination chemotherapy with one of the following regimens with or without PCI given to patients with complete responses:

The following regimens produce similar survival outcomes:

• 
  CAV: cyclophosphamide + doxorubicin + vincristine
  
• 
  CAE: cyclophosphamide + doxorubicin + etoposide
  
• 
  EP or EC: etoposide + cisplatin or carboplatin
  
• 
  ICE: ifosfamide + carboplatin + etoposide
  

Other regimens appear to produce similar survival outcomes but have been studied less extensively or are in less common use, including:

• 
  cyclophosphamide + methotrexate + lomustine
  
• 
  cyclophosphamide + methotrexate + lomustine + vincristine
  
• 
  cyclophosphamide + doxorubicin + etoposide + vincristine
  
• 
  CEV: cyclophosphamide + etoposide + vincristine
  
• 
  single-agent etoposide
  

2. Radiation therapy to sites of metastatic disease unlikely to be immediately palliated by chemotherapy, especially brain, epidural, and bone metastases.

Recurrent Small Cell Lung Cancer

The prognosis for small cell lung carcinoma that has progressed despite chemotherapy is exceedingly poor regardless of stage. Expected median survival is 2 to 3 months. These patients should be considered for palliative therapy or clinical trials. Patients who are primarily resistant to chemotherapy and those who have received multiple chemotherapy regimens rarely respond to additional treatment. However, patients who have initially responded and relapsed more than 6 months following initial treatment are more likely to respond to additional chemotherapy. While no single chemotherapy regimen should be considered standard, those that have shown activity as second line treatment include oral etoposide, etoposide/cisplatin, cyclophosphamide/doxorubicin/ vincristine (CAV), lomustine/methotrexate, and topotecan. A randomized comparison of second line treatment with either CAV or topotecan reported no significant difference in response rates or survival, but palliation of symptoms was better with topotecan.

Some patients with intrinsic endobronchial obstructing lesions or extrinsic compression due to tumor have achieved successful palliation with endobronchial laser therapy (for endobronchial lesions only) and/or brachytherapy. Expandable metal stents can be safely inserted under local anesthesia via the bronchoscope, resulting in improved symptoms and pulmonary function in patients with malignant airways obstruction. Patients with progressive intrathoracic tumor after failing initial chemotherapy can achieve significant tumor responses, palliation of symptoms, and short-term local control with external-beam radiation therapy. However, only the rare patient will experience long-term survival following "salvage" radiation therapy.

Patients with central nervous system recurrences can often obtain palliation of symptoms with radiation therapy and/or additional chemotherapy. The majority of patients treated with radiation therapy obtain objective responses and improvement following radiation therapy. A retrospective review showed that 43% of patients treated with additional chemotherapy at the time of CNS relapse respond to second-line chemotherapy.

Treatment options:

1. 
   Palliative radiation therapy.
   
2. 
   Salvage chemotherapy can provide some palliative benefit for patients previously sensitive to standard chemotherapy.
   
3. 
   Local palliation with endobronchial laser therapy, endobronchial stents, and/or brachytherapy.
   

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