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Resume Les auteurs rapportent l’observation d’une jeune femme âgee de 24 ans en remission complete quatre ans apres la fin d’un traitement pour un pneumoblastome biphasique. Apres une lobectomie inferieure gauche, la patiente a presente une recidive locale traitee par chimiotherapie. Cette observation est l’occasion de refaire le point sur les aspects cliniques, radiologiques et therapeutiques de ce type tres rare de tumeur maligne du poumon.

Resume Rationnel La chimiotherapie de seconde ligne (CSL) n’est pas validee dans le mesotheliome pleural malin (MPM). Dans notre experience, de nombreux patients en bon etat general au moment de la rechute sont pourtant candidats a un traitement de rattrapage. Methode Nous avons retrospectivement analyse notre experience en matiere de CSL dans le MPM dans deux centres parisiens de cancerologie thoracique (l’institut Gustave-Roussy, a Villejuif et l’hopital d’Instruction des Armees Percy, a Clamart). Resultats Pendant la periode du 1er janvier 2005 au 31 decembre 2006, nous avons collige 84 patients consecutifs, porteurs d’un MPM en progression apres une chimiotherapie de premiere ligne a base de pemetrexed. Un traitement de seconde ligne est administre a 44 patients (30 hommes et 14 femmes) qui presentent un âge moyen de 58 ans (extremes : 34 a 70 ans), un performance status (PS) inferieur ou egal a 1 dans 82 % des cas et une histologie epithelioide dans 91 % des cas. Le temps jusqu’a progression est egal a 6,1 mois. La mediane de survie est egale a 12,2 mois (extremes : deux a 72 mois). Secondairement, une troisieme et une quatrieme ligne de traitement ont ete realisees respectivement chez quatre et deux patients. Conclusions Dans notre experience, chez les patients ayant un MPM en rechute apres une premiere ligne standard a base de pemetrexed et en bon etat general, il est possible d’administrer un traitement de rattrapage. La CSL optimale n’est pas encore definie actuellement et des etudes prospectives sont necessaires dans ce cadre.

The respiratory infections are very frequent during lung cancer. Their diagnosis is often difficult because of the various etiologies (cancer, chemotherapy, radiotherapy) and this complexity can make discuss a preliminary bronchial exploration before any therapeutics. When it is about a located infection, germs in cause are often the same that in the community respiratory infections, in particular bacilli Gram negative, and it is thus logical to treat by the penicillin A. In front of an interstitial syndrome, it is necessary to evoke the opportunist infections, which are increasing in patients with cancer because of the multimodality therapeutic and the elongation of the survival. The neutropenic patient must be distinguished because of its specificities. The pulmonary infections lead to an important mortality. According to the patient (advanced age, underlying chronic obstructive pulmonary disease [COPD]) and to the treatment (chemotherapy, pneumonectomy), prevention must be discussed as the pneumococcal and Haemophilus influenzae vaccination.

Resume Le mesotheliome pleural malin (MPM) est une tumeur rare et incurable. Longtemps neglige, le MPM connait recemment un regain d’interet explique par l’augmentation reguliere de son incidence, temoignant d’une utilisation intensive de l’amiante, sa principale etiologie, mais aussi par une sensibilisation des milieux politiques et scientifiques confrontes a un veritable enjeu de sante publique. Le niveau des connaissances s’ameliore regulierement dans les domaines du diagnostic anatomo-pathologique et des mecanismes de la carcinogenese mesotheliale ; le MPM profite aussi d’innovations technologiques comme l’illustrent l’identification de marqueurs biologiques modernes, l’acces a l’imagerie metabolique et la recherche clinique sur les traitements cibles. La prise en charge du malade implique desormais la societe francaise toute entiere, depuis la mise en place de procedures d’indemnisation sociales. Surtout, une approche therapeutique plus volontaire se dessine en 2007 depuis la decouverte de chimiotherapies efficaces, l’optimisation des techniques de radiotherapie et l’emergence du concept de traitement multimodal centre sur la pleuropneumonectomie elargie. Ces avancees suscitent de reels espoirs, mais aussi beaucoup d’incertitudes, car aucun standard n’est encore clairement identifie.

Resume Les tumeurs epitheliales thymiques, regroupant les thymomes et les carcinomes thymiques, sont rares, de croissance le plus souvent lente, se developpant dans le mediastin anterieur. Les thymomes, en particulier, peuvent etre associes a des maladies auto-immunes et plus particulierement a la myasthenie. Leur traitement repose essentiellement sur une chirurgie complete. La radiotherapie postoperatoire y est systematiquement associee dans les thymomes invasifs avec atteinte des organes de voisinage ou dans les formes plus evoluees. Elle est en revanche plus discutee en cas de franchissement de la capsule. Dans les lesions d'emblee inoperables ou metastatiques, la chimiotherapie neoadjuvante a base de cisplatine a sa place, suivie d'une chirurgie maximaliste et d'une radiotherapie postoperatoire.

Resume Les immunonutriments presentent, associe a leur valeur energetique, une action pharmacologique propre. Les acides gras N-3 (AGN-3) grâce a leur action modulatrice de la reponse inflammatoire et a un eventuel effet antitumoral propre ont un role potentiel au cours de la prise en charge de la pathologie cancereuse. Les premieres etudes d'observation etaient prometteuses en montrant une diminution de la perte ponderale au cours de la prise en charge de certains cancers. Les etudes comparatives ulterieures n'ont pas reussi a confirmer cet effet favorable et a mettre en evidence un benefice en faveur de l'utilisation des AGN-3 par rapport a un groupe temoin. Cette discordance apparente, est la consequence des multiples differences qui existent entres les etudes dans : leur conception, les doses d'AGN-3 utilisees, la presentation pharmacologique, et les objectifs etudies. Neanmoins, certaines donnees semblent se degager : 1) il existe une relation dose–effet avec la necessite de prise importante d'AGN-3 ; 2) l'association avec certains acides amines favorise la synthese proteique et diminue la proteolyse ; 3) la compliance des patients avec une mauvaise tolerance digestive souvent responsable des sorties d'etude, est la difficulte majeure qui restreint l'utilisation de ces therapeutiques.

Resume Les cancers bronchiques a petites cellules (CPC) representent 20 % de l’ensemble des cancers bronchiques. Apres le bilan d’extension initial, seul un tiers de ces patients aura finalement une forme limitee. Le traitement des CPC limites repose actuellement sur les associations chimiotherapie-radiotherapie qui ont permis une amelioration de la survie globale et de la survie sans metastases au cours des dernieres annees. Neanmoins, meme dans les formes limitees, la survie a 5 ans varie entre 10 et 15 % et ne depasse guere 25 % dans les meilleures series. Le risque de rechute est en effet eleve : si pres de 70 % des patients avec une forme limitee parviennent a une reponse complete, seul 15 a 20 % d’entre eux survivront de facon prolongee. En effet, la plupart rechutent, et le risque de dissemination cerebrale par exemple est particulierement eleve, puisqu’il atteint pres de 50 % a 2 ans meme chez des patients mis en reponse complete. Ainsi, l’irradiation prophylactique cerebrale a egalement pris place dans la prise en charge standard des patients ayant un CPC en reponse complete suite aux resultats d’une meta-analyse ayant montre que la survie a 3 ans etait amelioree de 5 %. Malgre l’amelioration de la survie globale grâce aux traitements combines, les resultats mediocres observes en termes de survie a long terme devraient stimuler plus d’essais therapeutiques, afin de trouver les chimiotherapies et les modalites de radiotherapie optimales, la meilleure facon d’associer ces deux traitements ainsi que la place de nouvelles therapeutiques.

Due to their rarity, only few trials have studied the role of the doxorubicin-streptozotocin (DS) combination in advanced well-differentiated pancreatic endocrine carcinomas (AWDPEC). However, the published results are inconsistent. We reviewed all AWDPEC (5-year period, 45 patients) treated in our institution with the DS combination for: objective response rate (ORR), progression-free survival, overall survival (OS) and toxicity. An ORR of 36% (95% Confidence Interval (CI) 22-49) was obtained, with 16 partial responses (PR). The mean duration of PR was of 19.7 months. Two and 3-year OS rates were 50.2 and 24.4%, respectively. Toxicities were mainly digestive (grade > or =3 vomiting, 13%) and haematological (grade > or =3 neutropenia, 24%). Previous systemic chemotherapy and malignant hepatomegaly were associated with a poorer ORR (P=0.033, P=0.016) and OS (P=0.008, P=0.045). Multivariate analysis demonstrated previous chemotherapy as the only independent predictive-factor for survival (P=0.013). In conclusion, our data confirm the sensitivity of AWDPEC to the DS combination, with an ORR of 36% and a remarkable median response duration of 19.7 months, and suggests that it could be considered as a valid option in first-line therapy.

Background The aim of this study was to determine the toxicity profile, the recommended dose (RD) and the pharmacokinetic parameters, and to evaluate the antitumor activity of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer (NSCLC) and ovarian carcinoma (OC). Methods Gemcitabine was administered as a 30-min infusion followed by a 2-h infusion of oxaliplatin, repeated every 2 weeks. Doses of gemcitabine and oxaliplatin ranged from 800 to 1500 and 70 to 100 mg/m2, respectively. Results Forty-four patients (26 males, 18 females; median age 55 years) including 35 NSCLC (five platinum pretreated) and nine OC patients (all platinum pretreated) received a total of 355 cycles. All patients were evaluable for toxicity. No dose-limiting toxicity at any dose level occurred during the first two cycles; therefore, the highest dose-level of gemcitabine (1500 mg/m2) and oxaliplatin (85 mg/m2) was considered as the RD. Hematological toxicity was moderate amongst the 22 patients treated(167 cycles) at that dose level. Thirteen cycles were associated with grade 3–4 non-febrile neutropenia in six patients, and eight cycles with grade 3–4 thrombocytopenia in two patients. Other toxicities were mild to moderate, consisting of asthenia and peripheral neurotoxicity. Four of the 35 patients treated with oxaliplatin 85 mg/m2 experienced grade 3 neurotoxicity requiring treatment discontinuation at cycle 10. In the range of the doses used, gemcitabine and its main metabolite 2′,2′-difluorodeoxyuridine appeared not to be affected by oxaliplatin 70–100 mg/m2. Of the 44 patients evaluable for activity, 12 NSCLC patients experienced objective responses (one complete and 11 partial responses) and three OC patients showed tumor stabilization lasting for 6 months with a 50% decrease of CA 125 level. Two partial responses (NSCLC) and one tumor stabilization (OC) occurred in platinum-resistant patients. Conclusions The combination of gemcitabine and oxaliplatin could be safely administered on an out-patient schedule in patients with advanced NSCLC and OC. The RD was gemcitabine 1500 mg/m2 and oxaliplatin 85 mg/m2 every 2 weeks. Promising antitumor activity was reported in patients with NSCLC and platinum-pretreated OC, and thus, deserves further evaluation.

Summary Since the development of the first immunoassay for circulating chromogranin A in 1984, a lot of studies have evaluated its clinical impact in neuroendocrin e tumors. Initially studied in pheochromocytoma patients, the clinical impact of chromogranin A has rapidly extended to most neuroendocrine tumours, sometimes in combination with other eutopic or ectopic secretions. In our experience, CgA demonstrates a variable sensitivity between NET primary and a high specificity. Our results suggest that CgA should be routinely screened in foregut-derived NET and abandoned in the routine screening of medullary thyroid carcinoma. In addition, in phaeochromocy toma and ileumNET patients, CgA demonstrates a comparable sensitivity with urinary reference markers and its impact on the followup will form a key point when recommending routine screening. Both tumor burden and secretory activity should be taken into account when interpreting CgA results. Neuroendocrine tumors (NET) constitute a tumor network scattered in the body. They are characterized by common features including secretion of hormones, association as part of hereditary syndrome, impact of functioning imaging and, in one subgroup, poor aggressiveness. Secretion of hormones is a main feature of neuroendocrine tumors (NET) with multiple consequences for the diagnosis and prognosis of these tumors. Since 1984, the chromogranin A (CgA), a glycoprotein of the core of storage vesicles, has emerged as a potential general marker of these tumors [1]. CgA plays major roles in the storage and secretion of several hormones within the neuroendocrine cell vesicles. Furthermore, its impact on the pathological diagnosis of NET is well established [2]. This review article summarizes our experience with CgA measurement in the diagnostic biological work-up of NET.

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

Resume But de l'etude Rapporter les resultats des etudes CEBI 140 et CEBI 142. Le but de ces etudes etait d'ameliorer les taux de controle locoregional et de survie dans les carcinomes bronchiques non a petites cellules au stade III par une radio-chimiotherapie concomitante dans l'etude CEBI 140 et par une radio-chimiotherapie concomitante suivie d'une chirurgie dans l'etude CEBI 142. Materiel et methodes Trente-quatre patients qui avaient un carcinome bronchique non a petites cellules au stade III ont ete inclus dans l'etude CEBI 140 de decembre 1989 a decembre 1992. Les patients ont recu un traitement d'association comprenant du cisplatine administre de facon quotidienne (6 mg/m 2 par jour, 144 mg/m 2 au total), de la vindesine administree de facon hebdomadaire (2,5 mg/m 2 ,, 15 mg/m 2 au total) et une radiotherapie bifractionnee (60 Gy/48 fractions/6 semaines) suivie de deux cures de cisplatine (120 mg/m 2 a j18 et j45 apres la fin de la radio-chimiotherapie) et de trois cures de vindesine (6 mg/m 2 a j24, j31 et j38 apres la fin de la radio-chimiotherapie). Vingt-huit patients qui avaient un carcinome bronchique non a petites cellules de stade IIIB ont ete inclus dans l'etude CEBI 142 a partir de janvier 1993. Les patients ont recu un traitement d'association comprenant du cisplatine (100 mg/m 2 administres a j1 et j24, 200 mg/m 2 au total), de la vinblastine (4 mg/m 2 administree a j1 et j24, 8 mg/m 2 au total), du 5-fluorouracile en perfusion continue (1000 mg/m 2 administres de j1 a J3 et de j24 a j26, 6000 mg/m 2 au total) et une radiotherapie bifractionnee (deux series de 21 Gy a raison de 14 fractions sur 9 jours, les deux series etant espacees de 11 jours) suivie d'une exerese chirurgicale, apres une nouvelle evaluation. Resultats Dans l'etude CEBI 140, tous les patients ont recu la radiotherapie prescrite, mais la dose de cisplatine etait reduite dans 27 % des cas et celle de vindesine dans 88 % des cas. Il y a eu deux deces dus a une toxicite. Trois mois apres la fin du protocole, 50 % des tumeurs avaient completement repondu. Les taux de survie globale a 1, 2, et 3 ans etaient respectivement de 53, 33 et 11 %; les taux de survie sans signe evolutif etaient de 21, 11 et 11 %. Dans l'etude CEBI 142, la tolerance immediate a ete bonne. Vingt et un patients (75 %) ont ete operes. Quatre tumeurs n'ont pu etre excisees. La resection etait histologiquement incomplete chez un patient, et complete chez les 16 autres. Avec un recul median de 14 mois, dix patients etaient en vie sans recidive. Conclusion Les resultats preliminaires de l'etude CEBI 142 sont encourageants. Un plus grand nombre de patients traites et un suivi plus long sont cependant necessaires pour conclure. Il pourrait etre interessant de mettre en place un essai therapeutique controle comparant le protocole CEBI 142 et une radiotherapie classique.

Resume Le diagnostic de mesotheliome pleural epithelial est realise apres une thoracoscopie-talcage chez un homme de 58 ans qui presente une pleuresie. L’evolution est rapidement defavorable malgre une chimiotherapie systemique, avec des douleurs dorsales revelant un envahissement vertebral et du canal rachidien, responsable d’une compression medullaire 3 mois apres le diagnostic du mesotheliome.

Clinical trials investigating new trends in the treatment of stage I and II malignant mesothelioma have shown both intra-pleural immunotherapy and systemic chemo-immunotherapy to be efficacious. Intra-pleural gamma-interferon (γ-IFN) therapy was associated with tolerable toxicity and an overall response (ORR) rate of 19%, while treatment with intra-pleural recombinant interleukin-2 (IL-2) was more toxic, but yielded an ORR of 47% in phase I trial and 55% in a phase II study. The association of intravenous cisplatin and subcutaneous α-interferon (α-IFN) was also associated with an encouraging ORR of 40% and a median survival of 12 months. Treatment with cisplatin, α-IFN and mitomycin C was associated with moderate toxicity and an ORR of 21% and a median survival of 12 months. The association of cisplatin, α-IFN and IL-2 was, however, extremely toxic and resulted in an ORR of 15%. The majority of patients responding to intra-pleural immunotherapy and systemic chemo-immunotherapy had epithelial type mesothelioma. The most encouraging results obtained from trials investigating systemic chemotherapy were following treatment with cisplatin, 5-fluorouracil, mitomycin C and etoposide, where an ORR of 38% and an overall median survival rate of 16 months were achieved. Toxicity was mainly haematological and tolerable.

We report the results observed in a large randomized study comparing radiotherapy alone to combined radiotherapy and chemotherapy in unresectable squamous cell and large cell lung carcinoma. Radiation dose was 65 Gy in both groups and chemotherapy included vindesine, cyclophosphamide, cisplatin and lomustine. One hundred seventy-seven patients received radiotherapy alone, and 176 received the combined treatment. The 2-year survival rate was 14% for patients receiving radiotherapy vs. 21% for patients receiving the combined treatment (P = 0.02). The distant metastasis rate was significantly lower in the group receiving the combined treatment (P < 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively) and remains a major problem in locally advanced non-small cell lung cancer.

Two chemotherapy regimens for patients with extensive small-cell lung cancer were prospectively compared in a randomized multicentric trial with crossover. Every four weeks, 60 consecutive previously untreated patients received either DPE (doxorubicin, cisplatin and etoposide), or CIV (carboplatin, ifosfamide and vincristine) with crossover as soon as progression or end of response were observed. Pretreatment characteristics were similar in the two groups. Fifty-seven patients were evaluated for response. The response rate was higher with the DPE regimen both in first-line (for DPE: response rate 62% (18/29), including 17% (5/29) of complete response (CR), and for CIV: response rate 29% (8/28) with no CR, p < 0.02) and in second-line after crossover (for DPE: response rate 45% (9/20) including 5% (1/20) of CR, and for CIV response rate 0%, p < 0.02). Major toxicities were equally frequent in both groups. No significant difference was found between median survival times (9.7 months for the DPE group and 10.4 months for the CIV group). We conclude that: 1) DPE is a more active regimen than CIV, both in first- and second-line; 2) no alternating scheme may be considered with these two combinations. Of particular note is the similar median survival times in the two groups, contrasting with the different activities of the two regimens.

The authors report their experience with the MVP (mitomycin/vindesine/cisplatin) regimen of the Memorial Sloan-Kettering Cancer Center (MSKCC) which showed the highest response rate in non-small cell lung cancer (NSCLC). The aim was to respect the original reported schedule to appreciate its activity, because the same drug combination with dose and schedule variations used by other investigators has failed to reproduce the original report results. 82 consecutive previously untreated patients with unresectable and/or metastatic NSCLC received mitomycin (8 mg/m2 days 1, 29, 71), vindesine (3 mg/m2, days 1, 8, 15, 22, 29, 43, 57, 71) and cisplatin (120 mg/m2, days 1, 29, 71), with evaluation on day 71. 24 objective responses were noted (29%) (2 complete response/22 partial response) (95% CI 19%-39%), without differences according to histology. Differences in median survival were noted according to the performance status and type of response. Overall survival rates in responding patients were similar to those noted with the original schedules. Analysis of selection criteria showed that there were more patients with bone (P less than 0.01) or liver metastases (P less than 0.05), less women (P less than 0.001) and less adenocarcinoma (P less than 0.001) than the MSKCC trial. A dose intensity analysis showed only a minimal difference in the average weekly doses of vindesine (10% lower than MSKCC trial: 1.8 mg/m2 vs. 2.25 mg/m2). Disease improvement, a subjective response criterion used in the MSKCC trial, was probably underestimated in the current study. We conclude that the potential benefit of chemotherapy with a three-drug combination in NSCLC is greatest in patients with stage IIIa and IIIb disease or stage IV disease with a good performance status and a low metastatic volume.

48 patients with colorectal cancer metastatic to the liver were implanted with a subcutaneous access system allowing hepatic intra-arterial perfusion. Regional chemotherapy used 5-fluorouracil, while 17 patients also received low-dose mitomycin at the beginning of the study. Responses to the treatment occurred in 29 patients (60%) and median survival was 14.4 months. Toxicity included gastroduodenal erosions in 12.5% of the patients, leucopenia in 20.8%, catheter thrombosis in 42% and arterial thrombosis in 50%. 2 patients died of digestive haemorrhage probably related to treatment. When individually analysed, four factors were found to significantly affect survival: presence of hepatomegaly (defined as palpable liver edge exceeding the right costal margin by more than 5 cm) (P = 0.006), percentage of hepatic replacement superior to 50% (P = 0.003), more than four metastases (P = 0.025) and hypovascularised metastases at radionuclide liver scan with 99mtechnetium-labelled macroaggregate albumin (MAA) (P = 0.04). The effect of the four variables on the observed survival time was analysed using a Cox regression model. Two variables were found to have simultaneously influenced survival. Presence of hepatomegaly emerged as the more significant (P = 0.0001), the other being hypovascularised metastases at 99mTc-MAA.

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.

Les metastases intestinales (parietales et mesenteriques) ont le plus souvent une origine gastrique, ovarienne ou renale. Une tumeur primitive intra-thoracique telle qu'un cancer bronchique est parfois en cause [1]. Des metastases digestives peuvent etre egalement suspectees devant un tableau d'occlusion chez un malade ayant un mesotheliome pleural malin (MPM).

A 24-year-old man had a mediastinal embryonal carcinoma containing yolk sac foci. Combination chemotherapy with cisplatin, bleomycin, etoposide, and vinblastine was given, and the residual mass was then resected. Histology showed only necrotic cells. No other treatment was given. Two years later the patient presented with episodes of flushing and syncopes related to a systemicmastocytosis. Bone marrow examination showed a diffuse infiltration with large, atypical mast cells often with multilobulated nuclei. The patient suffered several episodes of cardiovascular collapse and died during one of these episodes, 8 months after the diagnosis of systemic mastocytosis and 40 months after the diagnosis of mediastinal tumor. Autopsy findings included the absence of mediastinal tumor and a diffuse liver and spleen mast cell infiltration. This was the second case with the similar clinicopathologic picture of two rare diseases being associated. This fact supports the hypothesis of a distinct entity, part of the mediastinal germ cell tumor/hematologic malignancy syndrome. The hypothesis of a cytokine secretion induced by mediastinal germ cell tumor supporting mast cell proliferation may be considered.

SO-CALLED “STATE-OF-ART chemotherapy” in advanced nonsmall cell lung cancer (NSCLC) is based on cisplatin (CDDP) and vinca alkakoids, such as vindesine (VDS) or vinblastine (VLB), or more recently, vinorelbine (VRL) [I, 21. On the basis of our recent experience with VDS continuous infusion (CI) and CDDP in metastatic small cell carcinoma of the head and neck [3, 41, we decided to explore the feasibility, tolerability and activity of CDDP plus CI VDS and 5-fluorouracil (S-FU) (FVP regimen) in NSCLC. A retrospective (historical) comparison has been done with the results obtained by our own group in a previous trial with the reference MVP (rnitomycin C, VLB and CDDP) regimen [5-8 1. From February 1989 to November 1989, 53 consecutive previously untreated patients bearing measurable or evaluable NSCLC were entered into the trial. Patients’ characteristics, stage and sites of metastasis are listed in Table 1. FVP regimen: 5-FU 800 mg/m* by 24-h CI, on days 1 to 4; VDS 0.8 mg/m2 by 24-h CI on days 1 to 4; CDDP 100 mg/m2 on day 1 with hydration and mannitol-induced diuresis. Both 5-FU and VDS were diluted in 1000 ml of isotonic solution and administered by a catheter placed in the subclavian vein. Cycles were repeatedevery 3 weeks. VDS and 5-FUdoses wereadjusted according to white blood cell (WBC) counts on days lo,14 and 20 after the previous cycle, with 20% reduction for grade IV myelotoxicity on days 10 and 14, and 50% reduction in cases of neutropenic fever.