Sequential administration of docetaxel followed by cisplatin-vindesine: a pilot study in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

In this phase II study, the feasibility and efficacy of sequential chemotherapy were tested with agents shown to be active as monotherapy. Patients with chemotherapy-naive, locally advanced or metastatic non-small cell lung cancer were selected for the study. Treatment involved four cycles of docetaxel (100 mg/m(2) on day 1, every 3 weeks) (sequence A), followed by four cycles of cisplatin-vindesine (cisplatin 120 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1, 8, 15, and 22, every 4 weeks) (sequence B). Responding patients received 3 cycles of docetaxel 100 mg/m(2) (day 1, every 3 weeks) as consolidation (sequence C). Thirty-two patients entered the study with thirty being evaluable for efficacy. Four patients showed a partial response and one patient a complete response, resulting in an objective response rate of 16.7 %. The median survival time (intent-to-treat) was 11 months (95 %CI = 8.0-15.4 months) with an estimated 1-year survival rate of 47%. The median time to progression was 17.6 weeks in the evaluable population. Main grade 4 toxicity was neutropenia (21.8 % and 68.2 % of patients in sequence A and B, respectively) while grade 3 peripheral neuropathy was documented in five patients during sequence B. There were no treatment-related deaths. Sequential chemotherapy may show promise for the treatment of advanced non-small cell lung cancer. Given the feasibility of this pilot study, sequential chemotherapy concept should be investigated with newer cisplatin-based regimens using this approach in larger prospective studies.

Radiation therapy for chordoma and chondrosarcoma of the skull base and the cervical spine. Prognostic factors and patterns of failure.

BACKGROUND: Prospective analysis of local tumor control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for chordoma or chondrosarcoma of the base of the skull and the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52 years (range: 14-85 years), were treated at the Centre de Protonthérapie d'Orsay (CPO), France, using the 201-MeV proton beam, 49 for chordoma and 18 for chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two thirds of the total dose and protons one third. The median total dose delivered within gross tumor volume (GTV) was 67 Cobalt Gray Equivalents (CGE; range: 60-70 CGE). RESULTS: Within a median follow-up of 29 months (range: 4-71 months), the 3-year local control rates were 71% and 85% for chordomas and chondrosarcomas, respectively, and the 3-year overall survival rates 88% and 75%, respectively. 14 tumors (21.5%) failed locally (eight within the GTV, four within the clinical target volume [CTV], and two without further assessment). Seven patients died from their tumor and another one from a nonrelated condition (pulmonary embolism). The maximum tumor diameter and, similarly, the GTV were larger in relapsing patients, compared with the rest of the population: 56 mm vs 44 mm (p = 0.024) and 50 ml vs 22 ml (p = 0.0083), respectively. In univariate analysis, age < or = 52 years at the time of radiotherapy (p = 0.002), maximum diameter < 45 mm (p = 0.02), and GTV < 28 ml (p = 0.02) impacted positively on local control. On multivariate analysis, only age was an independent prognostic factor of local control. CONCLUSION: In chordomas and chondrosarcomas of the skull base and cervical spine, combined photon and proton radiation therapy offers excellent chances of cure. In two thirds of the cases, relapses are located in the GTV. Maximum diameter, GTV, and age are prognostic indicators of local control. These results should be confirmed during a longer follow-up.

[Radiation therapy for chordomas and chondrosarcomas of the base of the skull and cervical spine]. / Irradiation par association de photons et de protons des chordomes et des chondrosarcomes de la base du crâne et du rachis cervical.

PURPOSE: Prospective analysis of local tumour control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for a chordoma or a chondrosarcoma of the base of the skull and of the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52.3 years (14-85), were treated using 201 MeV proton beam of the centre de protonthérapie d'Orsay (CPO), 49 for a chordoma and 18 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented 2/3 of the total dose and protons 1/3. The median total dose delivered within gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (60-70). RESULTS: With a mean follow-up of 32 months (4-71), the 3-year local control rates were for chordomas and chondrosarcomas of 70.8% and 85.2%, respectively and 4-year overall survival rates of 87.7% and 75%, respectively. Fourteen tumours (21.5%) failed locally (eight within the gross tumor volume, four into the CTV and 2 in an unknown site). Seven patients died of tumour and one of intercurrent disease. In univariate analysis, age inférieur ou égal à 52.3 years (p = 0.002), maximum tumoral diameter < 44.7 mm (p = 0.02) and GTV < 28.4 mL (0.02), at time of radiotherapy, influenced positively the local control. According to multivariate analysis, only age was an independent prognostic factor of local control. Only five (7.7%) patients presented grade 3 or 4 complications. CONCLUSION: In base of skull chordomas and chondrosarcomas, the combined photon and proton therapy offers excellent chances of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.