G. Krajnik

Neurological monitoring of neurotoxicity induced by paclitaxel/cisplatin chemotherapy

To evaluate the neurotoxicity of paclitaxel/cisplatin chemotherapy, we studied neurological and electrophysiological functions in 14 patients who had been treated with 1-7 courses of paclitaxel/cisplatin. The cumulative paclitaxel and cisplatin doses ranged from 175 to 1225 mg/m2 and 100-700 mg/m2, respectively. Neurological examinations as well as motor nerve conduction studies of the peroneal nerve were performed and summarised by means of a peripheral neuropathy score. Neurotoxicity with onset usually after the second treatment cycle occurred in 13 patients. 12 patients complained about sensory symptoms, 13 patients had impaired vibration sense and 8 patients developed additional muscle weakness, predominantly of the legs. Dysfunction of peroneal motor nerve conduction occurred in 13 patients. Reduction of amplitudes as well as slowing of conduction velocities were seen in 13 patients and prolonged distal latencies in 10 patients. The peripheral neuropathy score was elevated in 13 patients. Neurological symptoms, impairment of both vibration sense and tendon reflexes, and the peripheral neuropathy score increased with the cumulative doses of paclitaxel/cisplatin. Serial analysis among selected patients also revealed an increase in neurotoxicity with increasing cumulative drug doses. These data indicate the development of neurotoxicity in most patients treated with paclitaxel/cisplatin and also suggest that early signs of neurotoxicity can be detected by clinical examination with emphasis on symptoms as well as vibration sense and can be well documented by electrophysiological investigations.

Expertenempfehlung 2006 zur rationalen Zweitlinien-Therapie beim nicht-kleinzelligen Bronchuskarzinom

1 Medizinische Universität Innsbruck, Klinische Abteilung für Allgemeine Innere Medizin, Schwerpunkt Onkologie, Innsbruck, Österreich 2 KH der Elisabethinen Linz, Abteilung für Pneumologie, Linz, Österreich 3 Kaiser Franz Josef-Spital Wien, 3. Medizinische Abteilung – Zentrum für Onkologie und Hämatologie; LBI-ACR VIEnna & ACR-ITR VIEnna, Österreich 4 Klinikum Kreuzschwestern Wels, Abteilung für Lungenkrankheiten, Wels, Österreich 5 LKH Natters, Abteilung für Innere Medizin, Natters, Österreich 6 LKH Leoben, Abteilung für Lungenkrankheiten, Leoben, Österreich 7 Paracelsus Medizinische Privatuniversität, St. Johanns-Spital LKH Salzburg, Univ. Klinik für Innere Medizin III, Salzburg, Österreich 8 LKH Natters, Abteilung für Pneumologie, Natters, Österreich 9 Landesklinikum St.Pölten, 1. Medizinische Abteilung, St. Pölten, Österreich 10 LKH Feldkirch, Abteilung für Innere Medizin, Feldkirch, Österreich 11 SMZ West Baumgartner Höhe Otto Wagner Spital mit Pfelgezentrum, 2. Interne Lungenabteilung, Österreich 12 KH der Stadt Linz, Abteilung für Lungenkrankheiten, Linz, Österreich 13 Paracelsus Medizinische Privatuniversität, St. Johanns-Spital LKH Salzburg, Univ.-Klinik für Pneumologie, Salzburg, Österreich 14 Medizinische Universität Wien, Univ.-Klinik für Innere Medizin I, Wien, Österreich 15 Medizinische Universität Graz Univ.-Klinik für Innere Medizin, Klinische Abteilung für Onkologie, Graz, Österreich 16 LKH Feldkirch, Abteilung für Pneumologie, Feldkirch, Österreich 17 LKH Vöcklabruck, Abteilung für Innere Medizin, Vöcklabruck, Österreich 18 BKH Kufstein, Abteilung für Innere Medizin, Kufstein, Österreich

114 Vinorelbine/gemcitabine in advanced non-small-cell lung cancer (NSCLC): A phase I trial

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-naïve 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 30 mg/m2 and 600 to 1200 mg/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 25 mg/m2 vinorelbine combined with 1200 mg/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 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine on days 1, 8 and 15, but myelosuppression will have to be carefully monitored.

Multimodale Therapien bei bronchuskarzinomen

ZusammenfassungGrundlagenBei Patienten mit operablen Bronchuskarzinomen kommt es trotz Operation häufig zu lokalen und systemischen Rezidiven. Für die Prognose sind somit lokale und systemische Therapien von wesentlicher Bedeutung. Die Behandlung sowohl des nichtkleinzelligen als auch des kleinzelligen Bronchuskarzinoms erfolgt deshalb zunehmend mittels multimodaler Konzepte, die sowohl lokale Therapiemaßnahmen als auch die systemische Chemotherapie inkludieren.MethodikAls Lokaltherapie eignen sich die Operation und/oder Radiotherapie. Die systemische Chemotherapie erfolgt häufig mittels cisplatinhältiger Protokolle.ErgebnisseBei lokal fortgeschrittenen nichtkleinzelligen Bronchuskarzinomen kann die Prognose durch Induktionschemotherapien mit anschließender Operation im Vergleich zur alleinigen Operation verbessert werden. Auch die postoperative adjuvante Chemotherapie mit neuen Zytostatika und verbesserten supportiven Maßnahmen dürfte in Zukunft zu einer Verbesserung der Prognose bei Patienten mit operablen nichtkleinzelligen Bronchuskarzinomen führen. Das kleinzellige Bronchuskarzinom wird ebenfalls meist mittels multimodaler Konzepte, die die Operation in den Frühstadien inkludieren, behandelt.SchlußfolgerungenMultimodale Therapiekonzepte in Verbindung mit neuen Zytostatika und verbesserten supportiven Therapien dürften zu einer Verbesserung der Prognose von Patienten mit Bronchuskarzinomen führen.SummaryBackgroundTreatment of stage I–III lung cancer requires both local control of the disease and systemic treatment of micrometastatic disease. Thus multimodality treatment approaches are increasingly used for the treatment of lung cancer.MethodsLocal therapy includes surgery with and without radiotherapy. Systemic therapy is performed with preferentially cisplatin containing chemotherapy protocols.ResultsInduction chemotherapy with subsequent surgery has resulted in improved outcome of patients with stage III non-small cell lung cancer as compared to surgery alone. In patients with stage I–IIIA non-small cell lung cancer, postoperative adjuvant chemotherapy with better supportive care and new anticancer drugs might improve the survival of patients. Small cell lung cancer is also frequently treated by a multimodality approach that includes surgery in early disease stages.ConclusionsMultimodality approaches are increasingly used in the treatment of lung cancer and should improve the outcome of patients with lung cancer.

43 P - Paclitaxel/cisplatin in stage IIIB/IV non-small-cell lung cancer

Paclitaxel (Taxol ® ) as single agent has shown promising activity in advanced non-small-cell lung cancer (NSCLC). In our phase II trial, we have determined the efficacy of paclitaxel combined with cisplatin. Inclusion criteria were good performance status, adequate renal as well as bone marrow function and no prior chemotherapy. Patients with signs of severe cardiac or hepatic dysfunction, pregnancy, clinical manifest neuropathy or manifest cerebral metastasis were excluded. Twenty patients with histologically proven NSCLC stage IIIB or IV were treated with paclitaxel (175mg/m 2 ) as 3-hour infusion after standard premedication on day 1 and cisplatin (50mg/m 2 daily) on days 1 and 2 with antiemetic therapy and sufficient pre- and posthydration. Treatment cycles were repeated every 3 weeks. Progressive disease resulted in discontinuation of treatment. All 20 patients were evaluable for response and toxic effects. Partial responses were seen in 7 patients (35%), no change in 9 patients (45%) and progressive disease in 4 patients (20%). Major side effects included leukopenia (WHO Grade 4 in 1 patient), anemia, alopecia and dose-limiting neurotoxicity (WHO Grade 3 in 1 patient). No severe hypersensitivity reaction has been observed. Thus paclitaxel/cisplatin has shown good antitumor activity in patients with advanced NSCLC and should be further evaluated in this disease.

26 P - Monitoring of neurotoxicity of taxanes

Because the clinical use of taxanes migbt be limited by neurotoxicity, we have determined both clinical and electrophysiological neurological functions in 14 patients treated with paclitaxel/cisplatin (cumulative paclitaxel doses 175-1225 mg/m2, cumulative cisplatin doses 100-700 mg/m2) and in 6 patients treated with docetaxel (cumulative doses 100-400 mg/m2). Among the paclitaxel/cisplatin group, 12 patients developed sensory symptoms. Additional weakness was seen in 8 patients but motor nerve conduction studies of the peroneal nerve revealed impaired function in 13 patients. Three courses of docetaxel resulted in sensory neuropathy and a decrease in orthodromic sensory conduction velocity of the lateral plantar nerve in 3 patients. Docetaxel did not result in clinical motor neuropathy or altered motor nerve conduction of the peroneal nerve. In both groups, severity of clinical and electrophysiological neurotoxicity progrediently increased with cumulative drug doses. In conclusion, patients treated with paelitaxel/cisplatin developed sensory and motor neuropathy, whereas patients treated witb docetaxel only developed sensory neuropathy. Careful neurological and electrophysiological monitoring might allow to detect early symptoms of neurotoxicity and thus to avoid severe neurotoxicity.