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Biomedical subjects

J P Kleisbauer

Publications and source records attributed to J P Kleisbauer.

At least 19 recordsLinked to original sources
PubMed1999

Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.

PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.

Antineoplastic Agents↗
PubMed1999

[Long-term survival of a patient with melanoma with late recurrence of pulmonary metastasis treated by repeat surgery].

We report the case of a young woman initially treated with surgery, radiotherapy, chemotherapy and BCG therapy for stage II malignant melanoma involving the limbs. Considering that the risk of metastasis is usually maximal between 2 and 5 years after initial treatment, metastatic dissemination of this melanoma was rather unusual. Metastases were observed locally, regionally, and in the lungs 8, 10 and 12 years respectively after the primary diagnosis. Repeat surgery was performed to resect pulmonary nodules. Such surgery is possible in less than 10% of the cases of metastatic melanoma. Our patient has survived without relapse for 21 years after the initial diagnosis and 8 years after the last tumor excision. Recurrent pulmonary metastasis without extrapulmonary dissemination would suggest the tumor cell population was composed of a particular metastatic phenotype.

Aged↗
PubMed1998

Control of delayed nausea and vomiting with granisetron plus dexamethasone or dexamethasone alone in patients receiving highly emetogenic chemotherapy: a double-blind, placebo-controlled, comparative study.

BACKGROUND: The efficacies of granisetron plus dexamethasone and dexamethasone alone in controlling delayed nausea and vomiting after cisplatin chemotherapy (> or = 69 mg/m2) were compared in a multicentre, double-blind, placebo-controlled comparative study. PATIENTS AND METHODS: In all, 654 patients (of whom 619 were evaluable) received prophylactic granisetron plus dexamethasone before chemotherapy on day 0; on day 1 complete responders and non-responders were randomized separately to receive dexamethasone, 8 mg b.d. p.o., with either granisetron, 1 mg b.d. p.o., or matching placebo for six days. RESULTS: Over days 1-6 the complete response rates were 54.5% (dexamethasone group) and 52.1% (dexamethasone plus granisetron group). Response rates were higher over days 4-6 (71.8% and 70.7%, respectively) than over days 1-3 (60.4% and 57.9%, respectively). Significantly more patients who responded to antiemetic treatment during day 0 were responders over days 1-6 (63% vs. 17%; P < 0.001). No other treatment-related differences were found. Adverse events tended to be minor, with constipation and headache the most common. Overall, there were no significant differences in the safety profiles of the two regimens, but constipation and abdominal pain were significantly more common in the dexamethasone plus granisetron group. CONCLUSIONS: Granisetron plus dexamethasone did not appear to confer additional benefit over use of dexamethasone alone in controlling delayed nausea and vomiting following cisplatin chemotherapy. Control of acute nausea and vomiting, however, appeared to be an important factor influencing delayed nausea and vomiting.

Adult↗
PubMed1998

Granisetron plus methylprednisolone for the control of high-dose cisplatin-induced emesis.

This double-blind, double-dummy, randomized study compared the 24 h efficacy and safety of granisetron alone (3 mg i.v. over 30 s) or in combination with methylprednisolone (250 mg i.v. twice daily) in preventing nausea and vomiting in 308 patients (254 males) receiving high-dose cisplatin (100 mg/m2 or above) for mainly lung, and head and neck cancers. All patients received oral follow-on therapy comprising oral granisetron and methylprednisolone during the following 6 days. Primary efficacy variables were the proportions of complete responses (CR; no vomiting, no worse than mild nausea, no rescue and no withdrawal), no vomiting and no nausea over the first 24 h following initiation of the cisplatin infusion. The two treatment groups were well matched for demographics, cancer site, cisplatin dose and duration of infusion. Granisetron plus methylprednisolone was significantly more effective than granisetron alone for all primary efficacy variables: CR 78 versus 59% (p<0.001), no vomiting 80 versus 61% (p<0.001) and no nausea 74 versus 57% (p<0.002). Significantly more patients receiving the combination were free of any emetic symptoms (74 versus 54%, p<0.001). Significantly fewer patients receiving combination therapy also required rescue therapy with i.v. granisetron (12.2 versus 21.7%, p=0.026). During the follow-on period, complete response rates varied day by day from 50 to 71%. Both treatments were well tolerated, with constipation, abdominal pain and headache as the most frequent adverse events.

Abdominal Pain↗
PubMed1998

[Pleural effusion].

Bronchial cancer associated with a homolateral malignant pleurisy is classed as T4 whether the pleural disease is a direct extension or metastatic. Effusions without neoplastic cells do not enter into the TNM classification. Investigations of pleural disease consist initially of needle biopsies, completed sometimes by a thoracoscopy, which enable a precise staging and also the achievement of a pleurodesis. A review of the literature does not currently establish the value of a pleurectomy in cases of a homolateral effusion in bronchial carcinoma. Surgical excision may be carried out in a case of neoplastic pleurisy where no pleural invasion is found without knowing the benefits in terms of survival. The inverse exists, with local or diffuse pleural invasion without pleurisy, which are difficult to evaluate by imagery techniques. Thus certain authors recommend pleural lavage during surgical operations for bronchial cancer even without pleural disease: positive cytology seems to be a poor prognostic feature and would justify adjuvant treatment. Thoracoscopy should be carried out when the neoplastic nature of a pleurisy has not been established by needle biopsy in order to evaluate the resectability of the tumour in the absence of surgical contra-indication. In the case of a disabling neoplastic pleurisy a pleurodesis carried out at the time of pleuroscopy may avoid the recurrence of the effusion. Talc is most often employed for pleurodesis but Bleomycin or Tetracycline are also used. In the case of failure to re-expand a shrunken lung the failure of the pleurodesis may lead to a pleuroperitoneal shunt. The type of homolateral pleural disease in bronchial cancer with local invasion by contiguity as against pleural metastases should appear in the TNM classification because there are different treatments and also a different prognosis.

Biopsy↗
PubMed1997

Usefulness of longitudinal evaluation of Cyfra 21-1 variations in advanced lung cancer monitoring.

To investigate the usefulness of Cyfra 21-1 as an indicator of therapy effectiveness and prognosis in advanced primary lung cancer, sixty-three patients were selected on the basis of a high Cyfra 21-1 serum level (> 3.3 ng/ml) at the time of diagnosis. Serial assays of Cyfra 21-1 were performed during the first three courses of chemotherapy among 63 patients. The serial-values were analysed according to response to treatment and overall survival. After three courses of chemotherapy, a 70% reduction under the initial marker's value or a return to normal was observed for 36 patients. Twenty-two (61%) of these patients presented an objective response to therapy, making Cyfra 21-1 a moderate indicator in terms of positive predictive value (PPV). However, a significant decrease of Cyfra 21-1 was observed in 88% (sensitivity) of the 25 objective responders. Cyfra 21-1 changes after one course of chemotherapy (61 patients) were not sufficient to predict the future response after three courses (sensitivity 52%, specificity 56%, PPV 45%). Among 30 clinical or radiological relapses, a 10% increase or a return upper reference limit in Cyfra 21-1 level was observed in 18 cases (sensitivity 60%, specificity 100%, PPV 100%). Survival data were available for 61 patients. No significant statistical difference (P > 0.05) was found between survival curves depending on a significant decrease of Cyfra 21-1 after the first course of chemotherapy. We can conclude that the only interest of serial Cyfra 21-1 assays may be the detection of relapse, where one observes a significant decrease of the marker correlated with an objective response to first treatment.

Adult↗
PubMed1997

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.

Adult↗
PubMed1997

Long-term survivors of small-cell lung cancer (SCLC): a French multicenter study. Groupe d'Oncologie de Langue Française.

BACKGROUND: The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death. PATIENTS AND METHODS: Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review. RESULTS: Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age > 60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16-5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles > 6 (OR = 3.25, IC 95% (1.08-9.8) P = 0.02) and by an age > 60 (OR = 2.92, IC 95% (1.07-7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: age < or = 60 at the time of diagnosis (OR = 2.85, IC 95% (1.23-6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28-7.69), P = 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75-12.5), P = 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

Adult↗
PubMed1996

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.

Aged↗
PubMed1996

[Detection of human papillomavirus by polymerase chain reaction in primary lung carcinoma].

Human papillomaviruses (HPV) have been implicated in the pathogenesis of human squamous cell carcinoma, specially of cervical carcinomas. In previous studies concerning primary lung cancer, DNA of HPV subtypes was detected by in situ hybridization or polymerase chain reaction (PCR), up to 30% of the cases, namely in squamous cell carcinomas. A series of 31 frozen biopsies of lung carcinomas (surgical biopsies or through fiber optic bronchoscopy) were examined for the presence of HPV DNA by nested PCR. Primers for the two steps were type-specific primers (6/11-16 and 18; kit Amplicis-HPV) for the transforming region of HPV. HPV-DNA was found in five tumors: in two of 18 cases of squamous cell carcinoma (11%), in one of four cases of adenocarcinoma, in one of six cases of small cell carcinomas and in the unic case of neuro-endocrin carcinoma. No case of the two large cell undifferentiated carcinomas was positive. There were three cases of HPV 6/11, one case of HPV 16, and one sample positive for HPV 6/11 and HPV 18. No morphologic changes consistent with HPV lesions were observed. The frequency of 11% among the squamous cell carcinomas is near those found by previous studies (9 to 20% for HPV 6-11-16-18). For the first time, HPVs have been detected in neuro-endocrin tumors, and this have to be confirmed by studies of many more cases. So HPV might play a role as promoter in carcinogenesis of any types of lung carcinoma, although at a low frequency.

Adenocarcinoma↗
PubMed1995

[Carboplatin-VP16 combination in non small cell lung cancers in the aged patient. A study of the French group in pneumology (GFPC)].

UNLABELLED: Between February 1992 and May 1993, 22 patients older than 75 years, with non small cell lung cancer, were treated with carboplatin and oral etoposide. There were 18 men and four women with a median age of 79 years. Fourteen patients had an epidermoid carcinoma: four had an adenocarcinoma and four had an undifferentiated carcinoma. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2; oral etoposide was administered at a dose of 600 mg/m2 (two capsules daily) for 9, 10, 11, or 12 days according to body surface. Courses were repeated every 28 days for a total of three courses. TOXICITY: 15 patients (68%) had received previous chemotherapy. Myelosuppression was the main problem with one grade IV and five grade III hematologic toxicities. We observed one mild neurologic toxicity. RESULTS: 19 patients were evaluable for response. We observed one complete response (5%), five disease stabilizations (26%) and 13 disease progressions. Median survival was 5 months. These results led to discontinue this study.

Aged↗
PubMed1995

Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group.

The purpose of this study was to evaluate and compare the antiemetic effectiveness and tolerability of Navoban (tropisetron) and Zofran (ondansetron) following high-dose (> or = 50 mg/m2) cisplatin chemotherapy. In a randomised, multi-centre, double-blind, double-dummy, parallel group study, 117 evaluable chemotherapy-naive patients who received Navoban were compared with 114 who received Zofran. Patient diary cards were used to assess both acute (Day 1) and delayed (Days 2-6) nausea and vomiting. Total control of acute vomiting was achieved in 54% of Navoban and 65% of Zofran patients (p = 0.052), and total control of acute nausea in 66% and 62% respectively (p = 0.655). Total control of delayed vomiting was achieved in 44% of Navoban patients and 46% of Zofran patients (p = 0.765), and of delayed nausea in 56% and 47% respectively (p = 0.207). Both reactions combined were totally prevented during the entire 6-day trial period in 22% of Navoban and 24% of Zofran patients (NS), while a further 42% of patients in both groups remained largely free from both nausea and emesis. The few adverse reactions (e.g. headache, constipation, diarrhoea) were mainly mild and typical of the 5-HT3-receptor antagonists. In conclusion, there were no significant differences in efficacy and tolerability between Navoban 5 mg once daily and the highest recommended dose of Zofran (32 mg on Day 1, followed by 8 mg three times a day).

Antiemetics↗
PubMed1995

Combination chemotherapy with gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results of an ongoing phase I/II study.

Collaborative phase I and II studies of the combination of gemcitabine and cisplatin in patients with advanced non-small cell lung cancer are ongoing at five centres in the UK and France. In the initial completed phase I study, 16 patients (15 evaluable) have been entered using a fixed dose of gemcitabine 1000 mg/m2 given as a 30 min intravenous infusion weekly for 3 weeks. On the third week the gemcitabine was immediately followed by cisplatin with pre- and post-hydration. This regimen required only 1 night of hospitalization every 4 weeks. The study design was for sequential groups of patients to receive 3 dose levels of cisplatin (60 mg/m2, 75 mg/m2 and 100 mg/m2) but these doses would be modified and the number of patients at any dose level could be increased if significant toxicity was observed. Three patients were to be entered at the first two dose levels and 10 patients were to confirm the maximum tolerated dose (if reached) or expand the database on toxicity at the final predetermined dose level. The major haematological toxicities were neutropenia (grade 4 in 3 patients) and thrombocytopenia (grade 3 or 4 in 5 patients) but both were of short duration and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients but was no worse than would be expected from cisplatin alone. Alopecia was not a problem (no hair loss in 10 patients and grade 1 or 2 in 6 patients) and no significant renal or neurotoxicity was seen. A phase II study using cisplatin 100 mg/m2 in combination with gemcitabine 1000 mg/m2 has been opened and to date 19 patients are evaluable for response. Eight (42%) have achieved partial remissions. The study is ongoing and will recruit 50 evaluable patients.

Antimetabolites, Antineoplastic↗
PubMed1995

[Prognostic value of pre-therapeutic levels of carcino-embryonic antigen in primary bronchial carcinoma].

To evaluate the pronostic value of an elevated seric carcinoembryonic antigen (CEA > 10 ng/ml) at diagnosis, in patients with lung cancer, a pair study was done: couples of patients with same staging and histologic type were established, one patient with high CEA level compared to one patient with normal CEA level (< 5.5 ng/ml). Other markers were measured: neuron specific enolase (NSE), squamous cell carcinoma (SCC) or Cyfra 21-1. Survival was the end point of comparison. For 89 couples created, patients with low CEA level had a better survival rate at one year ( p = 0.02), this prognosis advantage was confirmed by a comparison of survival curves with Mantel-Cox and Breslow test (p = 0.01), but not by the signs test. These differences were also observed for the 71 couples of squamous cell carcinomas and adenocarcinomas, and the apparied signs test was still not significant. The poor prognosis persisted for patients with high CEA level, when one another marker's level (NSE or SCC or Cyfra 21-1) was increased, in comparison with patients with any marker increased. On 29 couples of all histological subtypes or on the 25 couples of non small cell lung cancer, the signs test and the comparison of survival curves were significant, but not the 1 year survival rate. This study shows that a CEA level greater than 10 ng/ml at diagnosis is a poor pronostic factor in patients with lung carcinoma, independent of the stage of disease and of the histologic type.

Antigens, Neoplasm↗
PubMed1995

Detection of human papillomavirus DNA in primary lung carcinoma by nested polymerase chain reaction.

Human papillomaviruses (HPV) have been implicated in the pathogenesis of human squamous cell carcinoma, especially of cervical carcinomas. In two previous studies concerning squamous cell carcinomas of the lung, DNA of HPV subtypes 6/11/16/18 (and 31/33/35 for one study) was detected by in situ hybridization in 7% to 30% of the cases. A series of 31 frozen biopsies of lung carcinomas were examined for the presence of HPVDNA by nested polymerase chain reaction (PCR). Type-specific primers (6/11, 16 and 18; Amplicis HPV(R)) located in the E6 or E7 transforming region of HPV were used. HPV DNA was found in 2 of 18 cases (11%) of squamous cell carcinoma, in 1 of 4 cases of adenocarcinoma and in 2 of 7 cases of neuro-endocrine cancers. The two large cell undifferentiated carcinomas were HPV negative. There were three cases of HPV 6/11, one case of HPV 16, and one sample positive for HPV 6/11 and HPV 18. No any consistent morphologic change with HPV lesions could be observed whereas squamous metaplasia could be seen only in squamous cell carcinomas. The frequency of 11% among the squamous cell carcinomas is comparable to those previously reported in studies utilizing in situ hybridization. To our knowledge HPV DNA had never been detected previously in adenocarcinomas or neuro-endocrine tumors. This finding should be confirmed by the investigation of larger series, but suggests that HPV could play a role in carcinogenesis of different types of lung carcinoma, although at low frequency.

Adenocarcinoma↗
PubMed1993

[Prognostic factors of lung cancer].

This subject interests the practitioner as it will enable him to predict, at the time of diagnosis, what are the chances for the treatment being successful, how long will the survival be, etc.? Unquestionable factors are the extent of the tumour expressed as stage, the number of metastasis sites and the histological nature of the cancer. Possible factors are: 1) In non-small cell carcinomas: Stage 1: P 53 mutation, satellite nodules found at surgery, tumour size less than 2 cm in diameter. Operated cancers: absence of invaded lymph nodes, small size of the tumour, mutation on P 185 Neu, codon 12 mutation of the cancer ras, mutation of P 53. Effectiveness of chemotherapy: positive NSE labeling. 2) Small cell carcinomas: extent of the lesions, number of metastasis sites and performance index. When these prognostic factors are known, they must be taken into account for the attempted treatments. On the other hand, factors of poor prognosis may influence the therapeutic approach.

Carcinoma, Non-Small-Cell Lung↗