Gemcitabine and small cell lung cancer

Abstract

Dear Sir, In most cases, small-cell lung cancer (SCLC) is an advanced and widespread disease at the time of diagnosis. The results of chemotherapy, which is the primary treatment modality, have remained disappointing and essentially unchanged over the past 10 years. The most effective polychemotherapy combinations for first and second-line therapy include cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PE), with nausea, vomiting, alopecia, nephrotoxicity, myelotoxicity, and neurotoxicity being the major adverse reactions [1]. A 62-year-old male (performance status, ECOG=0) was admitted to our department in June 1996 with SCLC that included bone-marrow metastasis. The disease was classified as right upper lobe SCLC, stage IV (T2N2M1). Since it was not eligible for surgery and/or radiotherapy, we commenced CAV chemotherapy. The patient was re-evaluated after receiving four treatment cycles and found to have a stable disease. Therefore, we opted for a second-line chemotherapy regimen, carboplatin plus VP-16, that was not cross-resistant with CAV. Carboplatin (300 mg/m) was administered every 21 days and 100 mg/m VP-16 was administered over days 1–3. Upon standard re-evaluation after three additional cycles, the patient still had a stable disease, with positive bone-marrow biopsies (T2N2M1). Because of the patient’s age and good performance status, we had to decide whether to continue this treatment regimen or administer a third-line monotherapy regimen that would minimize the toxic effects. Considering the limited survival time and general unresponsiveness to chemotherapy in advanced disease, and the toxic effects encountered after each chemotherapy cycle, we decided to proceed with third-line treatment using the novel agent, gemcitabine [2]; a 1000 mg/m dose was administered on days 1, 8, and 15 every 28 days. We initiated gemcitabine treatment on 18 April 1997, and continued to monitor the disease at the end of each cycle using chest X-rays and abdominal/pelvic sonograms. After six cycles, the patient was fully restaged. Again, there was no evidence of progression of the disease in other sites, including the brain; the primary lung tumour appeared stable and the bone-marrow biopsies showed ‘rare neoplastic, microcytoma-like cells’. On the basis of this finding, we no longer considered it necessary to monitor the disease at bone-marrow level. Gemcitabine therapy was continued and on 18 April 1998, exactly 1 year after starting the first cycle of gemcitabine, the patient completed the tenth cycle of treatment. During the treatment with gemcitabine, the patient did not experience any nausea/vomiting, asthenia/fever, or myelotoxicity that could compromise continuation of treatment. Unfortunately, 1 month after the tenth cycle, the patient showed brain metastases and died 2 months later. Because SCLC usually progresses to distant metastases, and the advanced stage of the disease is generally unresponsive to chemotherapy, the prognosis for this patient was poor. Gemcitabine, however, halted the progression of this highly aggressive disease without producing toxicity. It is also important to note that the patient was not chemonaive before receiving gemcitabine treatment [3]; he had undergone first-line therapy with multiple regimens including four cycles of CAV and second-line therapy with three cycles of carboplatin plus VP-16. The patient was able to complete ten cycles of gemcitabine, and then he died of brain metastases. Most importantly, during the gemcitabine treatment, there was no clinical evidence that would have contraindicated prolonged use of the drug. Gemcitabine’s ability to be administered in an ambulatory setting and its toxicity profile could translate into eco* Corresponding author. Present address: Via II Traversa Gran Sasso, 21, I-80026 Casoria (NA), Italy. Tel.: +39-081-566-5227; fax: +39-081-566-5230. E-mail address: mdvs.t@tiscalinet.it (M.D.V. Scarpati).