Objectives: Neoadjuvant therapy with a platinum based doublet is an option in NSCLC with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear.

Objectives Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear. Patients and methods In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction. Results After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively). Conclusion Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable.

Platinbasierte Zweierkombinationen gelten als Standardtherapie des fortgeschrittenen nichtkleinzelligen Lungenkarzinoms (NSCLC). Dreifachkombinationen führen möglicherweise zu einem besseren Ansprechen auf Kosten einer erhöhten Toxizität, während platinfreie Kombinationen bei besserer Verträglichkeit weniger effektiv sein könnten. Die vorliegende dreiarmige Phase III-Studie verglich eine platinhaltige Zweierkombination mit einer platinhaltigen Dreierkombination und einer platinfreien Sequenztherapie.

Authors G. Goeckenjan1, H. Sitter2, M. Thomas3, D. Branscheid4, M. Flentje5, F. Griesinger6, N. Niederle7, M. Stuschke8, T. Blum9, K.-M. Deppermann10, J. H. Ficker11, L. Freitag12, A. S. Lübbe13, T. Reinhold14, E. Späth-Schwalbe15, D. Ukena16, M. Wickert17, M. Wolf18, S. Andreas19, T. Auberger20, R. P. Baum21, B. Baysal22, J. Beuth23, H. Bickeböller24, A. Böcking25, R. M. Bohle26, I. Brüske27, O. Burghuber28, N. Dickgreber29, S. Diederich30, H. Dienemann31, W. Eberhardt32, S. Eggeling33, T. Fink34, B. Fischer35, M. Franke36, G. Friedel37, T. Gauler38, S. Gütz39, H. Hautmann40, A. Hellmann41, D. Hellwig42, F. Herth43, C. P. Heußel44, W. Hilbe45, F. Hoffmeyer46, M. Horneber47, R. M. Huber48, J. Hübner49, H.-U. Kauczor50, K. Kirchbacher51, D. Kirsten52, T. Kraus53, S. M. Lang54, U. Martens55, A. Mohn-Staudner56, K.-M. Müller57, J. Müller-Nordhorn58, D. Nowak59, U. Ochmann59, B. Passlick60, I. Petersen61, R. Pirker62, B. Pokrajac63, M. Reck64, S. Riha65, C. Rübe66, A. Schmittel67, N. Schönfeld68, W. Schütte69, M. Serke70, G. Stamatis71, M. Steingräber72, M. Steins73, E. Stoelben74, L. Swoboda75, H. Teschler76, H. W.Tessen77, M. Weber78, A. Werner79, H.-E. Wichmann80, E. Irlinger Wimmer81, C. Witt82, H. Worth83

PURPOSE:The purpose of the present phase 11 trial was to determine the efficacy and toxicity of vinorelbine-gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC).PATIENTS AND METHODS:From December 1997 to February 1999, 78 chemotherapy-naive patients (median age 60 years, Karnofsky performance status of 100, 90, 80 and 70 present in 5%, 41%, 36% and 18% of the patients, respectively) with stage IIIB (17%) or IV (83%) NSCLC (65% adenocarcinomas, 22% squamous-cell carcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas) received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a four-week cycle.RESULTS:In an intent-to-treat analysis, partial responses were seen in 19% of the patients. The median duration of response was 4.4 months. The median survival time was seven months and the one-year survival rate was 32%. Myelosuppression was the main side effect with WHO grade 3/4 neutropenia and thrombocytopenia in 35% and 11% of the patients, respectively. Other side effects were usually mild to moderate.CONCLUSIONS:Vinorelbine-gemcitabine is active, well tolerated and easy to administer on an outpatient basis in advanced NSCLC. Thus a randomized comparison of this combination with platinum-based protocols is warranted in patients with advanced NSCLC.

PURPOSE:To evaluate the feasibility of interferon gamma (IFNgamma) as an adjunct to chemotherapy in advanced non-small-cell lung cancer (NSCLC). METHODS:A total of 32 patients were recruited and received 25 mg/m2 cisplatin and 100 mg/m2 etoposide on days 8, 10 and 12 every 3 weeks for a total of three cycles. A dose of 100 microg IFNgamma was given subcutaneously three times weekly from days 1 to 8 and between days 15 and 29. After induction, all patients except those with progressive disease were offered IFNgamma maintenance therapy: 100 microg three times weekly. RESULTS:The following responses were obtained: partial response, 5 (16%); minor response, 12 (37%); stable disease, 4 (13%); progressive disease, 11 (34%). The survival rates after 1 and 2 years were 47% and 25% respectively. Patients receiving maintenance IFNgamma had a 2-year survival rate of 58%. Toxic side-effects were rare and included grade III/IV fever (7%/1%) and grade III/IV leucopenia (4%/1%). CONCLUSIONS:In patients with advanced NSCLC, an adjunctive dose of 100 microg IFNgamma, given three times weekly in the induction and maintenance phase, is feasible. Survival data seem favourable so this regimen may warrant further investigation in a phase III study.

Vinorelbine and gemcitabine are both active as single agents in advanced non-small cell lung cancer (NSCLC). Because of their different mechanisms of action, good tolerability and possible administration on an out-patient basis, vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy. Thus, we initiated a phase I dose-escalation trial in order to determine the maximum tolerated doses of vinorelbine/gemcitabine that can be administered without haematopoietic growth factors, the dose-limiting toxicities and the most frequent side-effects of this novel combination. 40 chemotherapy-naı̈ve patients with advanced NSCLC were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30mg/m2 and 600 to 1200mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received at least two treatment cycles. Dose-limiting toxicities were leucopenia plus thrombocytopenia (2 patients) and mucositis (1 patient). The maximum tolerated dose was established at 25mg/m2 vinorelbine combined with 1200mg/m2 gemcitabine. Frequent side-effects were leucopenia, anaemia, nausea/vomiting, flu-like symptoms, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20–25mg/m2 vinorelbine combined with 1000–1200mg/m2 gemcitabine on days 1, 8 and 15, but myelosuppression will have to be carefully monitored.

The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.