Lung cancer


treatment in small cell lung cancer

Despite treatment most patients with small cell lung cancer die of their disease. Treatment is generally aimed at palliating symptoms though significant prolongation of life can be obtained with relatively non toxic chemotherapy. As improvements in survival are going to be dependent on the development of new treatment strategies it is important that patients continue to be entered in appropriate clinical trials. With the increased evidence of response to chemotherapy in NSCLC and the interest generated by such advances, there has been less interest and therefore progress in the treatment of SCLC.

Treatment and prognosis in small cell cancer are not as dependent on locoregional tumor as is the case with non-small cell cancer as most patients have systemic metastatic disease at the time of diagnosis. Indeed, the patients performance status has more relevance to the treatment modality to which they are most suited. Disease is therefore classified as limited or extensive (Classification).

However, nonsurgical staging procedures allow an improved assessment of prognosis and identify sites of tumor that can be evaluated for response. They may also have treatment implications when chest irradiation is being considered. In those uncommon instances when surgery is an option as part of a combined modality program staging is performed in accordance with the TNM staging system for NSCLC (American Joint Committee on Cancer/UICC/IASCLC). In addition to the procedures in Table 7, a mediastinoscopy is virtually mandatory in this setting.

Standard regimes for treatment of small cell lung cancer include CAV (Cyclophosphamide, Doxorubicin and Vincristine) and ECMV (Etoposide, Cyclophosphamide, Methotrexate, Vincristine). These are well tolerated and have response rates in the region of 70%. They are administerd as outpatient regimes on a daycase basis. Side effects are usually moderate bone marrow toxicity. More recently the combination of a platin drug with etoposide (EP) has become the treatment of choice. These drugs show synergy in the laboratory and data on relapsed patients treated with this combination suggests the synergy is also present in vivo. As carboplatin requires no pre-hydration it is deliverable to outpatients so while being more expensive than cisplatin the carboplatin/etoposide regime has become the standard regime for good performance status small cell cancer patients. Increasing the dose and intensity of the standard drugs has not shown an improvement in survival. However, more intensive three and four drug combinations such as ICE or VICE (Vincristine, Ifosfamide, Carboplatin, Etoposide) are currently undergoing trials. These regimes have a higher toxicity but may have a more prolonged survival. Other new drugs to show response include topetecan and the taxanes, paclitaxel and docetaxel.

As most patients present with metastatic disease locoregional treatments play little part in treatment and systemic therapy is necessary. A small number of patients are suitable for surgery usually followed by chemotherapy. Local radiation may be indicated for emergency situations such as SVC obstruction or to areas less likely to respond to chemotherapy such as brain, epidural or bone metastsases.

Radiation to residual primary tumour is also used to consolidate chemotherapy. Improved survival has been reported in series investigating this approach. Interestingly the residual tumour may contain non-small cell elements not responsive to chemotherapy but sensitive to chemotherapy.

As the brain acts as a “sanctuary” site for metastatic disease cerebral metastases are common despite a good response of the main tumour to chemotherapy, prophylactic cranial irradiation (PCI) is often administered to those who have survived their chemotherapy and remain in good performance status. This reduces the incidence of brain metastases but there is debate over whether it improves survival. There is concern that cerebral irradiation may lead to brain damage. Neuropsychological deficit is not uncommon in small cell patients and there is no evidence that PCI adds to its severity.

Patients with poor performance status may not be able to tolerate the accepted regimes. They have a high incidence of infective complications particularly where segments of the lung are blocked causing obstructive pneumonitis. Various strategies have been tried to overcome these problems including the use of prophylactic antibiotics or using low dose chemotherapy for the initial cycles. A useful approach is to commence with the less toxic elements of a combination regime such as intravenous etoposide and add in the more toxic Platin agent if there is an increase in performance status. Oral etoposide has been used successfully in this group but its variable absorption has meant that it is unreliable when compared to standard regimes (such as CAV and ECMV) in patients who are fit enough to tolerate these drugs.