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1.
Rev Mal Respir ; 28(1): 97-100, 2011 Jan.
Article in French | MEDLINE | ID: mdl-21277483

ABSTRACT

INTRODUCTION: Pneumocystis pneumonia is a life-threatening infection in patients undergoing chemotherapy for solid malignancies. CASE REPORT: A 49-year-old man developed gradually increasing dyspnoea while receiving pemetrexed as a third line treatment for an adenocarcinoma of the lung. The diagnosis of pneumocystis pneumonia was based on ground-glass opacities on the thoracic CT scan and alveolar lavage revealing occasional cysts of Pneumocystis jiroveci in the context of recent lymphopenia developing during chemotherapy. Treatment with cotrimoxazole for three weeks was only partially successful due to progression of the tumour. CONCLUSIONS: Pneumocystis pneumonia should be considered in cancer patients receiving antifolate drugs and presenting with increasing dyspnoea. It is important to identify a high-risk population among patients undergoing chemotherapy because of the significant morbidity and mortality and in order to administer effective prophylactic agents.


Subject(s)
Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/toxicity , Glutamates/toxicity , Guanine/analogs & derivatives , Lung Neoplasms/drug therapy , Opportunistic Infections/diagnosis , Pneumocystis carinii , Pneumonia, Pneumocystis/diagnosis , Antifungal Agents/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/toxicity , Bronchoalveolar Lavage Fluid/microbiology , Disease Progression , Follow-Up Studies , Glutamates/therapeutic use , Guanine/therapeutic use , Guanine/toxicity , Humans , Infusions, Intravenous , Male , Middle Aged , Pemetrexed , Pneumonia, Pneumocystis/drug therapy , Retreatment , Tomography, X-Ray Computed , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
2.
Ann Oncol ; 14(8): 1291-8, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12881395

ABSTRACT

BACKGROUND: A randomized, multicenter phase II study evaluating oxaliplatin alone (OXA) and oxaliplatin-5-fluorouracil combination (OXFU) in advanced hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Metastatic, pathologically proven prostate carcinoma patients, progressing despite anti-androgen therapy, received intravenous OXA (130 mg/m(2 )over 2 h), alone or with 5-FU (1000 mg/m(2)/day, continuous intravenous infusion, days 1-4), every 3 weeks. OXA patients could receive OXFU after treatment failure. RESULTS: Fifty-four patients (26 OXA, 28 OXFU) from nine centers received 269 treatment cycles (106 OXA, 163 OXFU; median 3.5 OXA or 5 OXFU cycles per patient; range 1-10 or 1-14, respectively). Patient characteristics were similar in both arms. Three partial responses (PR) occurred in 21 evaluable OXA patients [14%; 95% confidence interval (CI) 1% to 30%], and in five of 26 evaluable OXFU patients (19%; 95% CI 7% to 39%). Clinical benefit response (pain, performance status and weight changes) was assessed in 20 OXA and 22 OXFU symptomatic patients, with more responders in the OXFU arm (39% compared with 12%). Median time to progression in the OXA and OXFU arms was 2.6 and 3.4 months, and median overall survival was 9.4 and 11.4 months, respectively. Hematotoxicity was common, but mostly mild to moderate. Neutropenia was more common in OXFU than OXA patients. After oxaliplatin failure, 12 patients received 46 cycles of OXFU and one of 11 evaluable patients had a PR. CONCLUSION: The objective response rate, palliation benefit, survival and manageable toxicity obtained in this heavily pretreated HRPC population with OXFU merit further study.


Subject(s)
Fluorouracil/administration & dosage , Neoplasm Invasiveness/pathology , Organoplatinum Compounds/administration & dosage , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Pyridines/administration & dosage , Adult , Aged , Antineoplastic Agents, Hormonal/administration & dosage , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm , Follow-Up Studies , Humans , Infusions, Intravenous , Male , Middle Aged , Neoplasm Staging , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/mortality , Risk Assessment , Salvage Therapy , Survival Rate , Treatment Outcome
3.
Ann Oncol ; 14(4): 603-14, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12649109

ABSTRACT

BACKGROUND: To assess the antitumour activity and safety profile of irinotecan and its pharmacokinetic interactions with anticonvulsants in patients with glioblastoma multiforme. PATIENTS AND METHODS: This multicentre phase II and pharmacokinetic study investigated the effects of irinotecan 350 mg/m(2) given as a 90-min infusion every 3 weeks either prior to (group A) or after relapse following radiotherapy (group B) in chemotherapy-naïve patients with glioblastoma. Preferred concomitant medication for seizure prevention was valproic acid. Pharmacokinetic analysis of irinotecan and its main metabolites (SN-38, SN-38-G, APC and NPC) was performed during cycle 1. An independent panel of experts reviewed the activity data. RESULTS: Fifty-two patients (25 patients in group A and 27 patients in group B) received a total of 191 cycles of irinotecan. Forty-six patients (22 patients in group A and 24 patients in group B) were evaluable and externally reviewed for activity. According to external review, one partial response (group B), seven minor responses (three in group A and four in group B), 12 disease stabilisations (seven in group A and five in group B) were observed. This resulted in an overall response rate of only 2.2% (95% confidence interval 0.2% to 6.5%). The median time to tumour progression was 9 weeks in group A and 14.4 weeks in group B. Six-month progression-free survival rates were 26% in group A and 43% in group B. Grade 3-4 toxicities (percentage of patients in groups A and B) consisted of neutropenia (12.5% and 25.9%), diarrhoea (8.3% and 7.4%), asthenia (12.5% and 7.4%) and vomiting (0% and 7.4%). The clearance of irinotecan was 12.4 and 14.4 l/h/m(2) in two patients who received no anticonvulsant. In patients receiving valproic acid, the clearance of irinotecan was 17.2 +/- 4.4 l/h/m(2). CONCLUSIONS: Irinotecan given at the dose of 350 mg/m(2) every 3 weeks has limited clinical activity as a single agent in patients with newly diagnosed and recurrent glioblastoma after radiotherapy. The toxicity profile and plasma disposition of irinotecan and SN-38 were not strongly influenced by anticonvulsant valproic acid therapy. Although the response rate of irinotecan as a single agent was limited, it remains an attractive drug for combination studies in patients with glioblastoma.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Brain Neoplasms/drug therapy , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Camptothecin/pharmacokinetics , Glioblastoma/drug therapy , Adult , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Camptothecin/adverse effects , Disease Progression , Drug Administration Schedule , Female , Glioblastoma/pathology , Glioblastoma/radiotherapy , Humans , Infusions, Intravenous , Irinotecan , Male , Middle Aged , Neoplasm Recurrence, Local , Neutropenia/chemically induced , Treatment Outcome , Vomiting/chemically induced
4.
Ann Oncol ; 11(1): 73-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10690391

ABSTRACT

PURPOSE: Gemcitabine and vinorelbine are active drugs with broad spectrum of activity and manageable toxicity in clinical trials. The aims of this study were to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of gemcitabine and vinorelbine to be recommended for phase II studies in patients with advanced cancers. PATIENTS AND METHODS: Drugs were given as 30-min infusions on day 1 and 8 (vinorelbine before gemcitabine) every 3 weeks. Thirty-six patients (male:female ratio 25:11; mean age 54, PS > 60) were treated including 1 retroperitoneal sarcoma, 7 head and neck, 10 lung, 4 thyroid, 6 pancreatic, 1 bladder, 2 ovary, 2 gastric, 1 rectum, 1 unknown primary, and 1 renal cell carcinoma. Doses of gemcitabine/vinorelbine ranged from 800/20 mg/m2 to 1500/30 mg/m2. RESULTS: The dose-limiting toxicity was neutropenia. A transient grade 2-3 elevation of transaminases was frequently observed at several dose-levels, although this toxicity did not appear to be dose dependant and was reversible at day 21 before the next cycle. Other toxicities were mild and easily manageable, consisting of fatigue and flu-like syndromes. Since the MTD was not reach at the higher dose-level, the recommended dose level of the gemcitabine-vinorelbine combination was 1500/30 mg/m2. One toxic death due to hematologic toxicity was reported in a heavily pretreated patient who underwent prior chemotherapy and pelvic radiotherapy. A total of 12 patients were treated at the recommended dose level which was associated with grade 3-4 neutropenia in 3 of 12 patients and in 22.9% of cycles. CONCLUSIONS: This study estimates that the recommended dose for phase II studies of gemcitabine-vinorelbine is 1500/30 mg/m2 at day 1 and 8 every three weeks. A careful monitoring of the hematologic toxicity is recommended in heavily pretreated patients and in patients who received pelvic radiotherapy. Partial responses observed in a patient with an advanced cisplatin-5-fluorouracil-resistant pancreatic adenocarcinoma and in a patient with mesothelioma support further evaluation of this combination in patients with tumors refractory to classical antitumor agents.


Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Deoxycytidine/analogs & derivatives , Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Deoxycytidine/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Leukocyte Count/drug effects , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Neoplasms/pathology , Platelet Count/drug effects , Vinblastine/adverse effects , Vinorelbine , Gemcitabine
6.
J Cancer Res Clin Oncol ; 122(9): 566-7, 1996.
Article in English | MEDLINE | ID: mdl-8781572

ABSTRACT

Perforation of the wall of the superior vena cava by a central venous catheter is reported. The resultant inadvertent infusion of 5-fluorouracil and epirubicin caused a severe acute inflammatory reaction in the right-lobe bronchus, mediastinal infiltration and pleural and pericardial effusions. The patient recovered but has residual mild oesophageal dysfunction.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Vena Cava, Superior/injuries , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Epirubicin/administration & dosage , Extravasation of Diagnostic and Therapeutic Materials , Fluorouracil/administration & dosage , Humans , Inflammation/chemically induced , Infusions, Intravenous , Male , Mediastinum
8.
J Cell Biol ; 131(3): 761-73, 1995 Nov.
Article in English | MEDLINE | ID: mdl-7593195

ABSTRACT

The NBT-II rat carcinoma cell line exhibits two mutually exclusive responses to FGF-1 and EGF, entering mitosis at cell confluency while undergoing an epithelium-to-mesenchyme transition (EMT) when cultured at subconfluency. EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from cellular cortex. The pleiotropic effects of EGF and FGF-1 on NBT-II cells suggest that multiple signaling pathways may be activated. We demonstrate here that growth factor activation is linked to at least two intracellular signaling pathways. One pathway leading to EMT involves an early and sustained stimulation of pp60c-src kinase activity, which is not observed during the growth factor-induced entry into the cell cycle. Overexpression of normal c-src causes a subpopulation of cells to undergo spontaneous EMT and sensitizes the rest of the population to the scattering activity of EGF and FGF-1 without affecting their mitogenic responsiveness. Addition of cholera toxin, a cAMP-elevating agent, severely perturbs growth factor induction of EMT without altering pp60c-src activation, therefore demonstrating that cAMP blockade takes place downstream or independently of pp60c-src. On the other hand, overexpression of a mutated, constitutively activated form of pp60c-src does not block cell dispersion while strongly inhibiting growth factor-induced entry into cell division. Moreover, stable transfection of a dominant negative mutant of c-src inhibits the scattering response without affecting mitogenesis induced by the growth factors. Altogether, these results suggest a role for pp60c-src in epithelial cell scattering and indicate that pp60c-src might contribute unequally to the two separate biological activities engendered by a single signal.


Subject(s)
Proto-Oncogene Proteins pp60(c-src)/physiology , Animals , Cell Movement/physiology , Epidermal Growth Factor/pharmacology , Fibroblast Growth Factors/pharmacology , Gene Expression/physiology , Growth Substances/physiology , Mutation/physiology , Rats , Transfection , Tumor Cells, Cultured/cytology , Tumor Cells, Cultured/enzymology , Urinary Bladder Neoplasms
10.
Bull Cancer ; 82(4): 292-5, 1995 Apr.
Article in French | MEDLINE | ID: mdl-10846539

ABSTRACT

Chemotherapy has little efficacy in the treatment of advanced colorectal carcinoma. Biological investigation has made evident several autocrine stimulation loops; the best documented one involves epidermal growth factor (EGF): this growth factor stimulates cell proliferation and cell secretion of proteolytic enzymes. Suramin and somatostatin are able to disrupt these loops of stimulation. Clinical studies performed with octreotide, a somatostatin analogue, and suramin have been unsuccessful until now.


Subject(s)
Cell Division/physiology , Colonic Neoplasms/pathology , Epidermal Growth Factor/physiology , Transforming Growth Factor alpha/physiology , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Humans , Neoplasm Invasiveness , Neoplasm Proteins/physiology , Somatostatin/therapeutic use , Suramin/therapeutic use , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/pathology
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