Teniposide sometimes effective in brain metastases from non-small cell lung cancer

Brain metastasis (BM) is a common complication of lung cancer, and is usually associated with a dismal outcome within a few weeks or months. Non-small cell lung cancer (NSCLC) comprises about 75% of all lung cancers. Recent epidemiologic data indicate that in the western world adenocarcinoma is replacing squamous cell carcinoma as the most frequent type. Adenocarcinoma tends to metastasize more often to the brain than the other histological types of NSCLC, thus being the primary tumor that is most frequently responsible for BM in patients with cancer.

Approximately 25% of patients with adenocarcinoma will develop clinical signs of BM during the course of disease. Usually BM is a part of systemic metastatic disease. In about 20% BM develop prior to or a few weeks after the diagnosis of the primary lung tumor. Particularly in adenocarcinoma BM may remain the only site of active metastatic disease.

Except from the occasional patient with an accessible solitary BM and absence of active systemic disease who will benefit from surgical resection, the standard treatment of BM from NSCLC consists of whole brain radiation therapy (WBRT) usually in combination with steroids. About 75% of the patients will show clinical improvement upon institution of steroids and RT. This palliation however is shortlasting (median of 2 months) and most patients will die with progressive, systemic disease after a median of 3 to 4 months. Those patients with an isolated recurrence in the brain suffer from progressive neurological dysfunction leading to death. Re-irradiation has not shown any benefit, although radiosurgery may be of benefit in exceptional cases.

Systemic chemotherapy is active against BM from small cell lung cancer (SCLC), but is generally considered not effective in BM from NSCLC. In recent years it has become apparent that a number of agents, including the podophyllotoxins etoposide and teniposide, may exert some activity in NSCLC. Intravenous teniposide at a standard dose of 150 mg/m2 is followed by a prolonged cytotoxic concentration in brain tumor tissue. With this background we have studied the efficacy of intravenous teniposide in patients with de novo and recurrent BM from NSCLC.

This study confirms the grim outlook for patients with NSCLC who develop BM. Although patients with the most unfavorable prognostic factors (uncontrollable extracranial tumor, impending brain herniation, low performance status) were excluded from this study, the median survival of the 7 patients with newly diagnosed BM was only 13 weeks. Only 2 patients survived more than 6 months despite additional WBRT after teniposide treatment in 4 of the 7 patients. The clinical improvement observed after steroids and systemic chemotherapy in 4 of 7 patients in the present study is in agreement with the response of BM from NSCLC following steroids and RT.

On the other hand this study shows that a subgroup of patients with NSCLC, may show a relatively favorable response to treatment of BM. In the 6 patients who were treated for recurrence of previously treated BM, the time to first relapse of BM amounted a median of 7 months. Particularly the cytostatic treatment of these relatively late relapsed BM seemed to result in substantial palliation: one patient survived systemic treatment of recurrent BM about one and a half year in complete neurological remission. However, also stabilization of the relapsed tumor mass by chemotherapy after initial steroid-induced clinical improvement, lead to a meaningful palliation, as shown in pt 9.



Boogerd, W., J. J. Van der Sande, and N. Van Zandwijk. “Teniposide sometimes effective in brain metastases from non-small cell lung cancer.” Journal of neuro-oncology 41.3 (1999): 285-289.