Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01).

BACKGROUND: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population. PATIENTS AND METHODS: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival. RESULTS: Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively. CONCLUSION: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

[Paraneoplastic sclerodermiform syndrome]. / Syndrome sclérodermiforme paranéoplasique.

INTRODUCTION: Despite the known association between scleroderma and cancer, the current systemic sclerosis classifications do not clearly identify paraneoplastic sclerodermiform syndrome or sclerodermiform syndrome secondary to cancer treatments. CASE REPORT: A 56 year old man was hospitalized for severe Raynaud's phenomenon with bilateral digital necrosis and otherwise good health status. X-rays did not show any subcutaneous calcification. Levels of serum antinuclear antibodies were high but anticentromere and anti-topoisomerase 1 antibodies were negative. Chest X-ray and CT-scan identified an irregular opacity in the right upper lobe with enlarged mediastinal lymph nodes. A diagnosis of bronchial adenocarcinoma was made following mediastinoscopy and the patient was treated with neo-adjuvant chemotherapy and lobectomy. After two cycles of treatment, his skin lesions had almost disappeared. CONCLUSION: The presence of a sclerodermiform syndrome may suggest the existence of an underlying neoplasm. In this case report, the skin lesions disappeared quickly after antineoplastic treatment. We suggest that sclerodermiform syndrome be included in the systemic sclerosis classification.

An open multicenter phase II trial of docetaxel-gemcitabine in Charlson score and performance status (PS) selected elderly patients with stage IIIB pleura/IV non-small-cell lung cancer (NSCLC): the GFPC 02-02a study.

UNLABELLED: The aim of this study was to determine the impact of patient selection based on age, comorbidity and performance status on the efficacy of platinum-free combination therapy on non-small-cell lung cancer after 65 years of age. We analyzed the overall response rate, the median survival time, the 1-year survival rate, toxicity and quality of life after one to three 6-week cycles of docetaxel 30mg/m(2) weekly and gemcitabine 900mg/m(2) at weeks 1, 2, 4 and 5. Fifty patients (median age 73.7 years) were eligible. The mean number of comorbid conditions per patient was 0.8 [Balducci L. Lung cancer and aging. ASCO 2005. Educational book. p. 587-91; Piquet J, Blanchon F, Grivaux M, et al. Primary bronchial carcinoma in elderly subjects in France. Rev Mal Respir 2003;20:691-9; Jatoi A, Hillman S, Stella P, et al. Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 2005;23:9113-9; Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000;5:224-37]. Forty-five patients were assessable: 17 (34%) had an objective response, 18 (36%) had stable disease and 10 progressed (20%). The median survival time was 7 months and the 1-year survival rate 23.5%. The main grade III-IV adverse event was neutropenia (32% of patients). CONCLUSION: Platinum-free dual-agent chemotherapy gives similar results in patients over 65, selected on the basis of their precise age and comorbidity, to that reported in younger subjects.

[Randomised phase II study evaluating oral combination chemotherapy (CCNU, cyclophosphamide, etoposide) and intravenous chemotherapy as second-line treatment for relapsed small cell bronchial carcinoma (Trial GFPC0501)]. / Etude de phase 2, randomisée, évaluant une polychimiothérapie orale (CCNU, Cyclophosphamide, étoposide) et une polychimiothérapie intraveineuse dans les cancers bronchiques à petites cellules en seconde ligne en rechute (essai GFPC0501).

BACKGROUND: There is no standard second-line treatment for small cell lung cancer (SCLC). The prognosis of these patients is poor and special attention should be paid to both quality of life and economic factors. METHODS: The aim of this phase II randomised trial (GFPC0501) is to compare, in patients with progressive SCLC after first-line platinum based chemotherapy, oral multi drug chemotherapy (CCNU, cyclophosphamide, etoposide) and classical intravenous chemotherapy with cyclophosphamide, doxorubicin and vincristine (CAV) in terms of tolerability, efficacy (response rate, median one year survival and overall survival), quality of life and consumption of health care resources. Based on a two-stage Bryant and Day approach, this study will require a total of 138 patients with an interim analysis of the first 38. EXPECTED RESULTS: This trial will provide information on several aspects of second-line chemotherapy for patients with SCLC. Thirty six patients have been enrolled in 16 centres by December 2006 and the results of the interim analysis will be available in June 2007.

Docetaxel and concurrent radiotherapy after two cycles of induction chemotherapy with cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer. A phase II trial conducted by the Groupe Francais de Pneumo-Cancerologie (GFPC).

CONTEXT: The most satisfactory treatment for patients with locally advanced non-small-cell lung cancer (NSCLC) is combination chemotherapy-radiotherapy (CT-RT). The optimal treatment modalities remain to be determined. OBJECTIVE: We conducted a multicenter phase II trial of the docetaxel-radiotherapy combination after induction chemotherapy with cisplatin-vinorelbine. The main endpoint was the objective response rate. PATIENTS AND METHODS: Patient with inoperable stage locally advanced NSCLC received induction chemotherapy consisting of two cycles of cisplatin 100 mg/m2 on D1 and vinorelbine 25 mg/m2 on D1, D8, D15 and D22. Patients with responses or stable disease then received concurrent RT-CT consisting of 25 mg/m2/week docetaxel and single-fraction radiotherapy (66 grays (Gy) in 33 fractions) over 6.5 weeks. RESULTS: Fifty-six patients were enrolled from 1 July 2000 to 31 December 2001. Sixteen patients left the trial after induction chemotherapy, eight for progression, five for toxicity, and two for intercurrent events. One patient underwent surgery after induction chemotherapy. In total, 40 of the 56 patients received RT-CT. Twelve (30%) of these 40 patients experienced grade III or IV pulmonary or esophageal toxicity. In the intention-to-treat analysis, the objective response rate was 46.4% (95% CI 33.0-60.2). The median time to progression was 6.2 months [1.1-26.0]. The median survival time was 13 months [0.3-44.9 months]. Nine patients progressed during RT-CT, six with brain metastases. CONCLUSION: Weekly docetaxel with concurrent radiotherapy, following chemotherapy is acceptable. The tumor response rate is moderate. Further trials are required to determine the risk-benefit relationship of this treatment schedule, and the possible benefit of adding other cytotoxic drugs.

Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1.

PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

[Phase II study of docetaxel in inoperable advanced non small cell lung cancer]. / Etude de phase II: docétaxel dans les cancers bronchopulmonaires non à petites cellules inopérables.

The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. / Efficacité du docétaxel dans les cancers bronchopulmonaires non à petites cellules antérieurement traités par une chimiothérapie comportant des sels de platine. Groupe Français de Pneumo-Cancérologie.

PURPOSE: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts. RESULTS: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes. CONCLUSION: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

A randomized clinical trial comparing concurrent and alternating thoracic irradiation for patients with limited small cell lung carcinoma. "Petites Cellules" Group.

BACKGROUND: Although thoracic radiotherapy is considered to be useful for the treatment of patients with small cell lung carcinoma (SCLC), its optimal administration schedule is still controversial. METHODS: In a multicenter clinical trial, 164 patients with limited SCLC (of whom 156 were eligible for the study) were randomized to receive either concurrent thoracic irradiation, initiated immediately after the second cycle of chemotherapy (Days 30-64) at a dose of 50 grays in 20 fractions, or alternating thoracic irradiation, scheduled in 3 courses between the second, third, fourth, and fifth cycles of chemotherapy with a 7-day rest period after and before chemotherapy at a dose of 20 grays in 8 fractions (Days 36-47 and Days 64-75) and then 15 grays in 6 fractions (Days 92-101). The same chemotherapy regimen (cyclophosphamide-doxorubicin or vindesine-etoposide) was administered every 4 weeks in both groups. RESULTS: Concurrent radiotherapy-induced lung toxicity led to early termination of this trial when a significant difference was observed (6 cases vs. 1, P = 0.05, 2-sided log rank test). Objective response rates were 89% in the 82 patients of the concurrent radiotherapy group and 95% in the 74 patients of the alternating radiotherapy group. Median survival periods were 13.5 and 14.0 months, respectively, with no significant difference between the two survival distributions (P = 0.15, 2-sided log rank test). Toxic deaths due to bone marrow hypoplasia were similar in both groups (3 vs. 2), but mortality due to lung toxicity (pulmonary fibrosis) was more frequent with concurrent radiotherapy (6 patients) than with alternating radiotherapy (1 patient) in long term analysis (P = 0.05, 2-sided log rank test). CONCLUSIONS: Although no statistically significant overall survival difference was observed between the two radiation therapy schedules, the better tolerance of the alternating schedule justifies the choice of this schedule with this chemotherapy regimen, although it may not be applicable to other chemotherapy regimens.

[High-dose ifosfamide in patients with stage IV non-small cell lung cancer: phase II trial from the Groupe français de pneumo-cancérologie (GFPC)]. / Ifosfamide à forte dose chez des patients porteurs de cancers bronchiques non à petites cellules de stade IV: essai de phase II du Groupe français de pneumo-cancérologie (GFPC).

PURPOSE: To assess the toxicity and efficacy of high dose ifosfamide in stage IV NSCLC. METHODS: In a previous trial, we have determined maximum tolerated dose for 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m2 according to hematologic tolerance. We therefore set up a phase II to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m2) was administered by a two hour infusion (3 g/m2) for three days every three weeks. Patients received three mesna bolus infusions (1 g/m2) at 4, 8 and 12 hours after the end of ifosfamide infusion. Antitumoral efficacy was performed after 2 cycles and treatment could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this study. Median age was 60.7 years +/- 1.33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, liver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudden death, 5 treatment interruptions before evaluation time and 3 toxic deaths (9.6%). TOXICITY: neutropenia grade 4 (10 pts and 1 death), cardiotoxicity grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3.6-29.8), 10 progressive diseases (32.3%, 95CI: 16.7-51.4) and 10 stabilizations (32.3%, 95CI: 16.7-51.4). Median response duration was 91 days +/- 55 d. Median survival was 9.3 months, e.g. 280 days (8-863). Overall survival at one year is 48%. CONCLUSION: This modality of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones could be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment on a 5-day schedule basis.

Prognostic significance of supraclavicular lymph nodes in small cell lung cancer: a study from four consecutive clinical trials, including 1,370 patients. "Petites Cellules" Group.

STUDY OBJECTIVE: To determine the prognostic significance of supraclavicular lymph node (SCLN) involvement in small cell lung cancer. MATERIALS AND METHODS: Patients (1,370) with small cell lung cancer were included in four consecutive clinical trials and classified as having either limited or extensive forms of disease using the Veterans Administration staging system. RESULTS: SCLN was present in 17% of patients (n = 234). Median survival was 258 days for patients with SCLN (n = 234) and 297 days for patients without SCLN (n = 1136) (p = 0.002). SCLN involvement was correlated with the presence of distant metastases at baseline (169 vs 65, p = < 0.001). Median survival was 375 days for patients with limited forms without SCLN (n = 529), 332 days for those with limited forms with SCLN (n = 65) (p = 0.12), 244 days for those with extensive forms without SCLN (n = 604), and 228 days for those with extensive forms with SCLN (n = 169) (p = 0.94). The 2-year survival rates were 17%, 12%, 2%, and 4%, respectively. Cox models confirmed that SCLN did not provide any significant additional prognostic information. CONCLUSION: SCLN is highly correlated with extensive forms explaining its overall prognostic value. In limited disease, SCLN is only a minor poor prognostic factor, not justifying any amendment to the staging system currently used.

Carboplatin as radiosensitizer in non-small cell lung cancer after cisplatin containing chemotherapy. A phase I study of a groupe francais de pneumo-cancerologie (G.F.P.C.).

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca aklaloïd. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to 15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time was 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.

Multicenter randomized trial comparing cisplatin-mitomycin-vinorelbine versus cisplatin-mitomycin-vindesine in advanced non-small cell lung cancer. 'Groupe Français de Pneumo-Cancérologie'.

The study was designed to evaluate the value of vinorelbine in a cisplatin-mitomycin-vinca alkaloid regimen for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). A group of 227 patients with inoperable NSCLC in stage III (58%) or stage IV (42%) were included in this randomized multicenter trial comparing a reference regimen (VDS group, n = 113) cisplatin (120 mg/m2 on day 1, day 29 and day 71), mitomycin (8 mg/m2 on day 1, day 29 and day 71) and vindesine (3 mg/m2/week for 5 weeks and then every 2 weeks up to the 15th week) to a cisplatin-mitomycin-vinorelbine combination (VNB group, n = 114), with cisplatin and mitomycin at the same doses, and vinorelbine 25 mg/m2/week for 16 weeks. The objective response rate (evaluated at 17th week) was 17% in the VDS group and 25% in the VNB group (P = 0.15). Median survival was 33.4 weeks and 34.5 weeks in the VDS and VNB arms, respectively. Overall survival duration was not significantly different between the two arms (logrank test, P = 0.20) despite a trend to an increased survival in the VNB group. This essentially benefited the patients with stage III disease with a clear-cut lengthening of median (45.9 vs. 33.4 weeks) and 1 year survival (44.6% vs. 26.2%, P < 0.05) in favor of the VNB group. Nevertheless, there was no significant difference in overall survival (logrank, P = 0.13). Survival duration of the patients with stage IV disease was comparable in the two arms (logrank test, P = 0.90). Grade 3 or 4 neutropenia was found in 61% and 87% of the VDS and VNB groups, respectively (P < 0.01). Grade 2-4 peripheral neuropathy was observed in 23% of the patients in the VDS group and in 6% of the patients in the VNB group (P < 0.01). Replacement of vindesine by vinorelbine in a cisplatin-mitomycin-vinca alkaloid chemotherapeutic regimen did not lead to a significant improvement in objective response rate or in duration of survival. There was a reduction in neurotoxicity at the expense of an increased hematologic toxicity. However, for patients with stage III disease there was an increase in 1 year survival with the vinorelbine combination.

[Recurrent pleural pericarditis]. / Pleuro-péricardite récidivante.

Primary pulmonary lymphoma is a rare disorder often clinically latent. We report a case of a pulmonary lymphoma diagnosed following a recurrent pleuro-pericarditis and its progress to a diffuse lymphoma of high-grade malignancy.

Dose optimization of gallium chloride, orally administered, in combination with platinum compounds.

An individual dose adaptation for cisplatin (CDDP), etoposide and gallium chloride (GaCl3) was proposed to improve the efficacy of this combination chemotherapy and avoid its toxicity. A clinical study was performed in 28 non small cell lung cancer patients, to verify this hypothesis. CDDP and etoposide were administered as continuous infusions every 3 weeks and GaCl3 orally during and between the CDDP-etoposide sequential infusions. CDDP doses were adjusted to achieve, during each 5 day infusion, an area under the total plasma platinum concentrations versus time curve (AUC Pt 0-120) ranging between 80,000 and 100,000 micrograms/l.h. Etoposide dosages were 120 mg/24 h during days 1-3 of the CDDP infusion. GaCl3 dosages were adjusted to obtain plasma gallium (Ga) concentrations ranging between 200 and 400 micrograms/l. The proposed methods of adaptation were successful from a pharmacokinetic point of view as AUC Pt 0-120 were respectively 81351 +/- 4788, 88268 +/- 8451 and 88331 +/- 8778 micrograms/l.h during the first 3 courses, and plasma Ga concentrations, determined during the 2nd and 3rd CDDP courses, 16 hours after the beginning of the CDDP infusion, were respectively 264 +/- 127 and 313 +/- 186 micrograms/l. However, these results were not pharmacodynamically successful and the therapeutic window was not confirmed. Past clinical trials with GaCl3 will be reviewed, as well as the factors which modify the pharmacokinetics or the pharmacodynamic effects of CDDP and GaCl3. From this review, an optimal dosage of 400 mg GaCl3 could be proposed to potentiate a combination chemotherapy with a platinum compound. The target AUC of the platinum compound should be the AUC avoiding its cumulative toxicity.

[Mediastinal bronchogenic cyst associated with a multiple malformation syndrome]. / Kyste bronchogénique médiastinal révélateur d'un syndrome polymalformatif.

The authors report a case of a patient presenting with a bronchogenic mediastinal cyst, which presented as a super-infection of the cyst. The cyst was associated with malformation of the cervical vertebra, cardiovascular abnormalities and congenital deafness, placing this in the group of rare complex polymalformation syndrome with Klippel-Feil Syndrome. The authors also stress the value of computed tomography, and above all of nuclear magnetic resonance in the analysis of mediastinal tumours and in particular, of bronchogenic cysts.