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Biomedical subjects

X Quantin

Publications and source records attributed to X Quantin.

14 recordsLinked to original sources
PubMed2000

Phase I-II study of high dose epirubicin plus cisplatin in unresectable non-small-cell lung cancer: searching for the maximal tolerated dose.

The purpose of this study was to search for the maximal tolerated dose of cisplatin in the cisplatin plus high-dose epirubicin combination for patients with non-small-cell lung cancer. The following range of cisplatin dosages were tested in a phase I study: 75, 90, 105, and 120 mg/m2 in combination with epirubicin 120 mg/m2 every 3 weeks. Eligibility consisted of previously untreated stage IIIb or IV non-small-cell lung cancers, Eastern Cooperative Oncology Group Performance Status less than or equal to 2, age less than or equal to 70 years, measurable disease, adequate blood counts, chemistry, cardiac function, and no brain metastasis. The maximal tolerated dose was defined as the dose level of cisplatin for which two of three patients or three of six patients developed one or more limiting toxicities during the first course of therapy. Afterward, the maximal tolerated dose of cisplatin was adopted in a subsequent phase II study. Three centers enrolled 42 patients: 18 in phase I and 24 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e., 120 mg/m2). Taking into account the total duration of the treatment, the real dose intensity for patients treated at the fourth dose level (120 mg/m2) did not differ from that of the third dose level (105 mg/m2). The latter dosage was therefore considered as the maximal tolerated one. In the subsequent phase II study, the median number of cycles received per patient was three (range: one to eight). Fifty percent required a dose reduction of either epirubicin, cisplatin, or both. The main toxicity was neutropenia, resulting in 10 episodes of febrile grade IV neutropenia requiring readmission. Other toxicities were mild to moderate. There was no toxic-related death. On intent-to-treat analysis, 10 patients (33%) achieved an objective response. Among them were three complete responders. Median survival was 8 months. We observed neither detraction nor improvement of quality of life as assessed using the European Organization for Research and Treatment of Cancer QLQ-C30-LC13. Given every 3 weeks in combination with epirubicin 120 mg/m2, the maximal tolerated cisplatin dose is 105 mg/m2. This combination yields activity in non-small-cell lung cancer.

Adult↗
PubMed1999

Concomitant brain radiotherapy and vinorelbine-ifosfamide-cisplatin chemotherapy in brain metastases of non-small cell lung cancer.

AIM: To determine whether or not brain radiotherapy and concomitant three-drug chemotherapy is feasible and yields anti-tumour activity in patients with non-small cell lung cancer and brain metastases at time of presentation. PATIENTS AND METHODS: Twenty-three previously untreated patients suffering from non-small cell lung cancer and brain metastasis were prospectively included in this feasibility study. Most of the patients had neurological symptoms and an Eastern Collaborative Oncology Group (ECOG) performance index over 2. Treatment consisted of three courses of whole brain radiotherapy (18 Gy in 10 fractions) and vinorelbine, 30 mg/m2 on days 1 and 8, ifosfamide, 1.5 g/m2 daily from day 1 through day 3 with uromitexan uroprotection, and cisplatin, 100 mg/m2 on day 2. A cycle restarted every 28 days. RESULTS: Eighteen patients completed the three-cycle programme. All patients were affected by a grade 4 neutropenia and 14 of them experienced a febrile episode. Other toxicities were mild to moderate and manageable. Received-dose intensities of vinorelbine, ifosfamide and cisplatin were 80, 90 and 90%, respectively. Overall response rate was 30%. Specific evaluation of brain response demonstrated complete response for seven patients, and partial response in six (objective brain response rate, 56%). All responders benefited by a remission of symptoms and improvement of performance index. Median survival from start of protocol was 7.6 months. CONCLUSION: Although the high rate of toxicity requiring re-admission, concomitant brain radiotherapy plus vinorelbine, ifosfamide and cisplatin chemotherapy is feasible in patients suffering from brain metastasis, and demonstrates an anti-tumour activity for this particular subset of stage IV non-small cell lung cancer. The development of such an aggressive approach needs further comparative evaluation.

Adult↗
PubMed1999

Neoadjuvant etoposide, ifosfamide, and cisplatin followed by concomitant thoracic radiotherapy and continuous cisplatin infusion in stage IIIb non-small cell lung cancer.

OBJECTIVE: To determine the applicability and safety of an ifosfamide, cisplatin, and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant thoracic radiotherapy and cisplatin continuous infusion in locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients (stage IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection), and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic support using recombinant human methionyl granulocyte colony stimulating factor. Patients who achieved a response or a stabilization were planned to receive a split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4-week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6 mg/m2 daily was administered using an autonomous chemotherapy delivery device. Total plasma platinum titration was performed daily during the two courses in five of the patients. Analyses were done on an intent-to-treat basis. RESULTS: Thirty-nine of the 44 patients received the three-cycle chemotherapy program. Received dose intensity was 82%. Thirty-eight patients received the radiotherapy and, among them, 35 received the complete concomitant continuous cisplatin infusion. Objective (complete) response rates were 48% (7%) at the end of chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end of the first radiotherapy cycle, the mean total plasma platinum concentration was twice as high as that of the residual postinduction chemotherapy concentration. During induction chemotherapy, myelosuppression was the limiting toxicity requiring hospital readmission in 23 patients. During radiotherapy, the main toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was observed using the subjective objective management analytic--late effects of normal tissue score without life-threatening pulmonary function impairment. None of the patients died from toxic reactions. Probability of survival at 1, 2, and 3 years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local relapse in 63% of the patients, brain metastases in 24%, and hematogeneous metastases to other sites in 13%. CONCLUSION: Neoadjuvant VIP followed by concomitant radiotherapy-chemotherapy is feasible, but the split-course radiotherapy did not prevent a high rate of local recurrences. The high rate of toxic reactions requiring hospital readmission limits further development of such an aggressive regimen in NSCLC.

Adult↗
PubMed1998

Predictive factors of tumor response and prognostic factors of survival during lung cancer chemotherapy.

The aim of this study was (i) to determine predictive factors of a complete response to chemotherapy in small cell lung cancer (SCLC) and predictive factors of an objective response in non-small cell lung cancer (NSCLC) and (ii) to determine whether prognostic factors are different with regard to treatment response and survival. Ninety-nine patients with SCLC and two hundred and two patients with NSCLC received chemotherapy. The following variables were recorded prior to treatment: tumor, node, metastasis status, performance status, body weight loss, blood leukocyte count, serum sodium, serum albumin, lactate dehydrogenase (LDH), alkaline phosphatase, serum NSE, serum TPS, and serum CYFRA 21-1. Tumor response was analyzed at the 10th week. Analysis of survival were done using the landmark method. Hazard ratios of the significant prognostic variables of survival were calculated using the Cox's model. Odds ratios of the significant predicting factors of response were calculated by stepwise logistic regression. In SCLC, the significant determinants of poor survival were: lack of complete response (HR: 2.04), weight loss (HR: 1.76), high serum LDH level (HR: 1.64), and high serum TPS level (HR: 2.47). A high serum TPS level was the only factor among those studied able to predict lack of achievement of complete response (OR: 0.39). In NSCLC, significant determinants of poor survival were: no objective response (HR: 2.28), poor performance status (HR: 2.52), presence of metastases (HR: 1.51), and high serum CYFRA 21-1 level (HR: 1.84). On the other hand, a high serum TPS level (OR: 0.50), the presence of metastases (OR: 0.45), and a leukocyte blood count over 10,000/microl (OR: 0.43) were independent determinants for a patient not to achieve an objective response. We concluded that the predictive factors of complete response in SCLC remain to be defined. On the other hand, in NSCLC three variables contribute to the prediction of an objective response. Finally, determinants of survival differ from predictive factors of response.

Analysis of Variance↗
PubMed1998

[Biological perspectives].

The tumour biology of non-small cell bronchial cancer integrates recent developments and a dynamic schema of the phenomena of tumour progression and diffusion of the metastatic disease. There is no leap of known biological disruption between Stage II and Stage III. The latter is defined by anatomical criteria and is a transition in the continuum of the natural history of these cancers. The moto for the tumour progression is the genotypic instability and phenotypic diversification. Metastatic microscopic disease constitutes the first cause of failure in the treatment of Stage III non-small cell bronchial cancer. Among prognostic factors for survival emphasis is placed on the alterations of p53 expression, different types of aneuploidy, anomalies of the expression of cellular adhesion molecules and finally, tumour diversification towards a metastatic phenotype.

Aneuploidy↗
PubMed1998

[Neuron-specific enolase (NSE) in the surveillance of small cell cancers. An evaluation of the prognostic information using Markov's model].

RATIONALE: An elevated serum NSE concentration is generally a bad prognostic sign when a diagnosis of small cell lung cancer is made. However, the marker may vary from time to time crossing the discriminant threshold (12.5 ng/ml) in one direction or the other. These variations are presumed to reflect the progress of the disease but it has not been shown that the risk of death from the disease is changed by alterations in the serum concentration of NSE. To resolve this question we have used Markov's mathematical model (homogeneous over time and in three states). METHOD: A prospective study has included 52 patients suffering from small cell cancer and treated with chemotherapy based on cisplatin. The NSE was measured following each treatment and three monthly in subsequent follow up. Markov's model was studying the intensities of transition and the risks of death between the two following transient states: living with an NSE concentration of < or = to 12.5 ng/ml, living with an NSE concentration of > 12.5 ng/ml, and an absorbing state: death. RESULTS: When a level of > 12.5 ng/ml was noted the mean time of maintaining in this state was short (123 days). During this time when a transfer was effected in 44 per cent of cases there is turn towards the opposite state (living with a concentration < 12.5 ng/ml) showing the real reversibility between the two transient states. When a patient had an elevated concentration of serum NSE the risk of death was 2.23 times greater than in the opposite state (living with a low NSE; P < 0.01). CONCLUSION: The observation of an elevated NSE concentration at any time in the follow up of patients suffering from small cell cancer was strongly associated with an elevated risk of death but a return from this state towards a state of less risk (living with a low NSE level) remains possible. This works suggests that the NSE levels may be useful in the follow up of small cell lung cancer.

Antineoplastic Agents↗
PubMed1998

[New cytotoxics in the treatment of bronchial cancers].

This review presents a synthesis of published studies on the activity of the newer cytotoxic drugs in the treatment of bronchial cancer. It also touches on the early indications of recent results which until now have only been the subject of oral presentations. The taxanes form a new class of anti-cancer drug. Myelosuppression is their limiting factor. These are very active cytotoxic drugs but their toxological profile makes them difficult to use in polychemotherapy. The anti-tumour activity of docetaxel (Taxotere) has been shown. For non-small cell cancer (CNPC) the objective response (OR) is of the order of 26% in new patients and 21% in those who have been pre-treated with a combination of drugs based on Cisplatine. For paclitaxel (Taxol) the OR is around 25% in new patients. In association with a course of cisplatine the efficacy would be dose dependent. For small cell cancer (CPC) it enables a level of OR around 38% as monochemotherapy. Inhibitors of topoisomerase I (topotecan, irinotecan) form another new class of therapy. Myelosuppression again limits their toxicity. Diarrhoea is an additional toxicity of irinotecan (Campto). The inhibitors of topoisomerase I seem particularly active as monochemotherapy in the treatment of smal cell cancer. Haematological toxicity makes them difficult in association. The activity of topotecan (Hycantin) in the treatment of non-small cell carcinoma remains to be studied. For this indication irinotecan would enable an OR of 33% in new patients. The new anti-metabolite, gemcitabine (Gemzar) is characterised by a different mode of action from other cytotoxics used in the treatment of bronchial cancer. For non-small cell carcinoma it is active as monotherapy and in association with cisplatine. Its activity is more modest in the treatment of CPC but few studies are available for this indication. Its toxic profile makes it promising to be used in association. The new spindle drug vinorelbine (Navelbine) is active as monotherapy or associated with cisplatine in the treatment of non-small cell carcinoma. The limiting toxicity is haematological. Its neurotoxicity is moderate compared to agents in the same therapeutic class. These different cytotoxic drugs arouse a ligitimate interest but the optimal therapeutic schemas for their use remain poorly understood (with the exception of vinorelbine). Their place in the therapeutic arsenal remains to be defined whilst waiting for the results of Phase III studies, their routine use cannot be recommended.

Antineoplastic Agents↗
PubMed1997

Concomitant brain radiotherapy and high-dose ifosfamide in brain relapses of lung cancer.

PATIENTS AND METHODS: Twenty patients with lung cancer and brain metastasis were prospectively included in this feasibility study (four small-cell and 16 non-small-cell lung cancers). There were two previously untreated patients and 18 pretreated patients for whom brain metastases constituted the first relapse after a treatment-free interval following chemotherapy for the primary lung cancer. Most of the patients had neurological symptoms and an ECOG performance index over 2. Treatment consisted of three courses of whole brain radiotherapy (18 Gy in 10 fractions) and ifosfamide: 3 g/m2 daily from day 1 through day 4, i.e., during the first four days of radiotherapy with uromitexan uroprotection and haematopoietic support (r-HuG-CSF). RESULTS: Seventeen patients completed the three-cycle programme. Sixteen patients had grade 4 neutropenia and six of them experienced a febrile episode. Other toxicities were mild to moderate and manageable. The received dose-intensity of ifosfamide was 90%. Response evaluation demonstrated stable disease for two patients, partial response for eight, complete response for six and progression for four. All responders benefited by a remission of symptoms and improvement of performance index. Median survival from start of protocol was 13 months. CONCLUSION: Brain radiotherapy plus high-dose ifosfamide is feasible in patients suffering from brain recurrences of lung cancer.

Adult↗
PubMed1997

Immunohistochemical detection of p53 protein and prognosis of surgically resected non-small-cell lung cancer.

We analyzed the survival of 89 surgically treated patients presenting non-small-cell lung cancer in regard to the accumulation of p53 protein as detected by indirect immunoperoxidase reactivity of PAb1801 anti-human p53 protein. Although the well-known factors such as stage grouping, tumor status, and nodal status were found to be prognostic determinants, the p53 protein accumulation had no effect on either univariate analysis or multivariate analysis of survival.

Adult↗
PubMed1996

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers.

One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete resection were prospectively entered in a study whose aim was to determine the prognostic significance of a hypodiploidy or a multiploidy pattern of tumour cell DNA content and a high immunohistochemical reactivity of Ki-67, a nuclear antigen related to the cell cycle. Indirect immunoperoxidase reactivity of Ki-67 on frozen tumour tissue sections was evaluated both visually, using a classical semiquantitative scale, and by means of a computer-assisted image processor. Cell DNA content analysis was done using static computer-assisted cytometry on tumour cytological prints stained by the pararosaline Feulgen-Schiff technique. The ploidy was characterised for each tumour by DNA index (DI), percentage of hypodiploid cells and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid and multiploid). Ki-67 immunostaining was negative in 64 tumours (48%) and positive in 69 (52%). DNA histogram classification disclosed 57 (42%) near diploid tumours. Among the 80 (58%) aneuploid tumours, 16 were hypodiploid, 44 hyperdiploid and 20 multiploid. The prevalence of both a positive Ki-67 immunostaining and an aneuploid DNA histogram differed according to histology as SCLC demonstrated a higher frequency of both features when compared with NSCLC and carcinoid tumours. On the other hand, Ki-67 immunostaining and ploidy did not significantly differ according to degree of differentiation, nodal status and Mountain's stage grouping. The percentage of cells in the hypodiploid modal DNA was significantly higher for tumours which demonstrated a high Ki-67 immunostaining, suggesting a link between growth fraction and DNA content abnormalities. In univariate analysis, survival did not differ significantly according to either the Ki-67 immunohistochemical reactivity or the DNA index. Patients with a hypodiploid tumour had a shorter survival than patients with other DNA histogram patterns but, owing to the low frequency of hypodiploidy, this difference did not reach statistical significance. In Cox's proportional hazard model, an SCLC histology, an advanced tumour status, a positive nodal status and a hypodiploid tumour (hazard ratio: 2.070; 95% confidence interval 1.041-4.116) were significant determinants of survival. We conclude that hypodiploidy in lung cancer is a distinct DNA content abnormality as it contributes significantly to prognosis. Neither visually assessed nor computer-generated Ki-67 immunostaining measurements significantly determine prognosis.

Adult↗
PubMed1996

Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21-1 and TPS.

We examined two recently described cytokeratin markers, CYFRA 21-1 (cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensitivity-specificity relationship, as analyzed by receiver operating characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in comparison with TPS in both small-cell and non-small-cell lung cancers. Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the highest in squamous-cell carcinomas (0.61) and the lowest in small-cell lung cancers (0.36), whereas sensitivity of TPS did not vary significantly according to histology (overall sensitivity, 0.40). In non-small-cell lung cancers, both serum CYFRA 21-1 and serum TPS distributions varied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse each above-mentioned variable became, the higher the median and interquartile serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In both small-cell and non-small-cell lung cancers, univariate survival analyses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L significantly indicated a poor survival rate. In the whole population, taking into account other significant variables, Cox's model analysis demonstrated that a poor performance index, an advanced stage of the disease, the presence of metastases, elevated serum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval, [1.33-2.27] were independent prognostic variables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.

Adult↗