Biomedical subjects

R S Marks

Publications and source records attributed to R S Marks.

At least 19 recordsLinked to original sources

PubMed2006

Luminescent yeast cells entrapped in hydrogels for estrogenic endocrine disrupting chemical biodetection.

In the construction of luminescent yeast cell based fibre-optic biosensors, we demonstrate a novel approach for estrogenic endocrine disrupting chemical (EDC) biodetection by entrapping genetically modified Saccharomyces cerevisiae cells, containing the estrogen receptor alpha-mediated expression of the luc reporter gene, in hydrogel matrices based on calcium alginate or PVA. In order to insure a significant signal, an optimal immobilization ratio of 1:2 alginate 3% (w/v): 5 x 10(6) [cells/ml], respectively, was used with the highest 17-beta-estradiol (beta-E2) induction factor after 2.5 h of incubation with 10[nM] beta-E2. It was shown that biocompatible alginate beads, 4.27-4.55 x 10(5) [CFU/bead], which were characterized by a detection limit of 0.08[microg l(-1)] and an EC50 of 0.64[microg l(-1)] for beta-E2, retained their viability for luminescence measurements after 1 month of storage at -80 degrees C slow freeze condition, and thus repeated cell cultivations were not required. The assay reproducibility for each tested EDC, represented by the coefficients of variation (CV), ranged from 4.35 to 18.47%. An alternative immobilization method, based on a room temperature partial drying of polyvinyl alcohol (PVA) solution (LentiKat Liquid) and cell suspension mix, was investigated with only a slightly lower detection limit for beta-E2 than that reported with alginate beads. Alginate yeast based hydrogels may also be applicable to the analysis of environmental water samples since the trend of detected estrogenic activities with alginate beads roughly correlated with LC-MS-MS analytical results.

Biological Assay↗

PubMed2005

Optical fiber immunosensor based on a poly(pyrrole-benzophenone) film for the detection of antibodies to viral antigen.

We describe herein a newly developed optical microbiosensor for the diagnosis of hepatitis C virus (HCV) by using a novel photoimmobilization methodology based on a photoactivable electrogenerated polymer film deposited upon surface-conductive fiber optics, which are then used to link a biological receptor to the fiber tip through light mediation. This fiber-optic electroconductive surface modification is done by the deposition of a thin layer of indium tin oxide on the silica surface of the fiber optics. Monomers are then electropolymerized onto the conductive metal oxide surface; thereafter, the fibers are immersed in a solution containing HCV-E2 envelope protein antigen and illuminated with UV light (wavelength approximately 345 nm). As a result of the photochemical reaction, a thin layer of the antigen becomes covalently bound to the benzophenone-modified surface. The photochemically modified fiber optics were tested as immunosensors for the detection of anti-E2 protein antibody analyte that was measured through chemiluminescence reaction. The biosensor was tested for sensitivity, specificity, and overall practicality. Our results suggest that the detection of anti-E2 antibodies with this microbiosensor may enhance significantly HCV serological standard testing especially among patients during dialysis, which were diagnosed as HCV negative, by standard immunological tests, but were known to carry the virus. If transformed into an easy to use procedure, this assay might be used in the future as an important clinical tool for HCV screening in blood banks.

Benzophenones↗

PubMed2004

Environmental tobacco smoke exposure in women with lung cancer.

BACKGROUND: Investigations on environmental tobacco smoke (ETS) exposure that include source intensity, childhood exposure, and association with histologic subtypes among never smoking lung cancer cases are limited. We report the patterns of ETS exposure history in a clinical cohort of women with newly diagnosed lung cancer. METHODS: From 1997 to 2001, 810 women with lung cancer were interviewed to obtain data including the source, intensity, and duration of ETS exposure. In this descriptive study, relationships between smoking history, ETS exposure, and lung cancer histologic subtypes were analyzed. RESULTS: Among the 810 patients, 773 (95.4%) reported personal smoking or ETS exposure including 170 of 207 (82%) never smokers. Among the never smokers with a history of ETS exposure, the mean years of exposure were 27 from a smoking spouse, 19 from parents, and 15 from co-workers. For each major subtype of lung cancer (adenocarcinoma, squamous cell, unclassified non-small cell lung cancer, small cell, or carcinoids) among never smokers, 75-100% of patients had ETS exposure. Trends for adenocarcinoma, squamous, and small cell carcinoma are statistically significant using the Cochran-Armitage Test for Trend (P<0.001) among never smokers without ETS exposure, never smokers with ETS exposure, former smokers, and current smokers. CONCLUSIONS: Over 95% of women with lung cancer in our study were exposed to tobacco smoke through a personal smoking history or ETS. The cumulative amount of tobacco smoke exposure may be significantly underestimated if only personal smoking history is considered. Our results add to the public health implications of exposure to tobacco smoke and highlight the importance of eliminating tobacco smoking in public and private settings.

Adult↗

PubMed2002

The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer.

This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 285 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men.

Adult↗

PubMed2001

Mediated electrochemical detection of catechol by tyrosinase-based poly(dicarbazole) electrodes.

A new dicarbazole derivative functionalised by an N-hydroxysuccinimide group has been synthesised and electrochemically characterised. Upon oxidative electropolymerisation of this monomer in organic electrolytes, electroactive poly(dicarbazole) films were formed on platinum electrodes. The subsequent chemical grafting of tyrosinase on the poly(dicarbazole) film was easily performed by immersion in an enzymatic aqueous solution. The amperometric response of the resulting biosensors to catechol has been studied at -0.2 V vs. saturated calomel electrode (SCE). Since the reduction of quinone generates radicals which may induce electrode fouling, thionine, a phenothiazine dye, was covalently bound to the poly(dicarbazole) backbone as it mediates the reduction of quinoid products and therefore induces an enhancement of the performance of the tyrosinase-based biosensor.

Anti-Bacterial Agents↗

PubMed2001

A phase II trial of edatrexate, vinblastine, adriamycin, cisplastin, and filgrastim (EVAC/G-CSF) in patients with non-small-cell carcinoma of the lungs: a North Central Cancer Treatment Group Trial.

Edatrexate is an antifolate agent with improved in vitro antineoplastic activity as compared with methotrexate. A Mayo phase I trial of edatrexate (E), vinblastine (V), doxorubicin (Adriamycin) (A), cisplatin (C), and filgrastim (GCSF), (EVAC-GCSF) showed promising antineoplastic activity in non-small-cell lung cancer (NSCLC) (Colon-Otero G, et al. Cancer J Sci Am 1997;3:297-302) leading to a phase II trial of this regimen, the results of which are reported here. A total of 34 patients with stage IIIB or IV measurable or evaluable NSCLC were entered in this North Central Cancer Treatment Group phase II study. Treatment consisted of edatrexate 100 mg/m2 intravenously on day 1 and cisplatin 30 mg/m2/d on day 1 and day 2 followed by vinblastine 3 mg/m2 intravenously and doxorubicin 30 mg/m2 intravenously on day 2. Filgrastim was given at 300 microg subcutaneously daily from day 4 to day 18 or until an absolute neutrophil count of 2,000/mm3 or more was obtained. Cycles were repeated every 21 days until either progression or the development of intolerable toxicity. Sixteen of 34 evaluable patients responded to therapy, for a response rate of 47.1% with a 95% CI of 30.3% to 63.8%. Median time to disease progression was 132 days, median survival time was 219 days, and the estimated 1-year survival was 41.2% (95% CI of 27.6-61.5%). The EVAC/G-CSF regimen has significant antineoplastic activity as seen by the response rates for patients with NSCLC. However, this study had significant myelosuppressive toxicity; 56% patients had grade III or higher leukopenia with three treatment-related deaths observed. In addition, Quality of Life assessments indicate that patients experienced an overall decline in quality of life during the course of treatment. These mitigating factors need to be considered regarding further evaluation of this regimen in this patient population.

Adult↗

PubMed2001

Long-term results of a phase I/II study of high-dose thoracic radiotherapy with concomitant cisplatin and etoposide in limited stage small-cell lung cancer.

This report presents the results from a Mayo Clinic initiated phase I/II study exploring a potentially more aggressive local and systemic approach for treatment of limited-stage small-cell lung cancer (LSSCLC). Five patients with LSSCLC received three cycles of induction cyclophosphamide, etoposide, and infusion cisplatin chemotherapy. This was followed by accelerated hyperfractionated thoracic radiotherapy (AHFTRT) consisting of 30 Gy given as 1.5-Gy fractions twice daily with a 2-week break and then the AHFTRT was repeated. The AHFTRT was given concomitantly with daily oral etoposide and daily intravenous cisplatin. Prophylactic cranial radiation was delivered with the AHFTRT. After completion of the AHFTRT, patients received 4 cycles of oral etoposide maintenance chemotherapy. Follow-up of patients was continued until death or a minimum of 42 months. Three patients had severe toxic responses. No patients completed the entire protocol because of toxicity or progression during treatment. Three patients completed the majority of the protocol except for the four cycles of maintenance etoposide. Four of five patients achieved a complete response. There were two recurrences within the irradiated field, and distant metastases developed in four patients. Acute nonlymphocytic leukemia developed in one patient, who died 2 months later. No patient completed the entire protocol, because of toxicity or progression; therefore, this protocol cannot be recommended for the treatment of LSSCLC.

Adult↗

PubMed2000

A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity.

Farnesyl protein transferase (FT), an enzyme that catalyzes the first step in the posttranslational modification of ras and a number of other polypeptides, has emerged as an important target for the development of anticancer agents. SCH66336 is one of the first FT inhibitors to undergo clinical testing. We report a Phase I trial to assess the maximum tolerated dose, toxicities, and biological effectiveness of SCH66336 in inhibiting FT in vivo. Twenty patients with solid tumors received 92 courses of escalating SCH66336 doses given orally twice a day (b.i.d.) for 7 days out of every 3 weeks. Gastrointestinal toxicity (nausea, vomiting, and diarrhea) and fatigue were dose-limiting at 400 mg of SCH66336 b.i.d. Moderate reversible renal insufficiency, secondary to dehydration from gastrointestinal toxicity, was also seen. Inhibition of prelamin A farnesylation in buccal mucosa cells of patients treated with SCH66336 was demonstrated, confirming that SCH66336 inhibits protein farnesylation in vivo. One partial response was observed in a patient with previously treated metastatic non-small cell lung cancer, who remained on study for 14 months. This study not only establishes the dose for future testing on this schedule (350 mg b.i.d.) but also provides the first evidence of successful inhibition of FT in the clinical setting and the first hint of clinical activity for this class of agents.

Adult↗

PubMed2000

Significance of neuron-specific enolase levels before and during therapy for small cell lung cancer.

The level of serum neuron-specific enolase (NSE) has been implicated as a prognostic factor for patients with small cell lung cancer (SCLC). A prospective evaluation was undertaken to assess the prognostic significance of pretreatment NSE and treatment-induced minimum NSE values in patients with SCLC. Patients from two Phase III North Central Cancer Treatment Group trials [one for patients with extensive stage SCLC and one for patients with limited stage SCLC] were asked to enter this laboratory correlational trial. Both trials included treatment with four to six cycles of etoposide and cisplatin, and 121 patients (71 extensive stage SCLC and 50 limited stage SCLC) were entered into the present study of NSE. Pretreatment NSE values and treatment-induced minimum NSE values were independent predictors of time to progression and survival in multivariate analysis. Hazard rate modeling allowed the formulation of specific relationships of NSE to time to progression and survival. Pretreatment NSE levels inversely correlated with time to progression and survival in these patients with SCLC. Pretreatment NSE accounted for 28% of the variance in survival. Both pretreatment NSE and treatment-induced minimum NSE were independent prognostic predictors of time to progression and survival.

Adult↗

PubMed1999

Chemotherapy for advanced CNS ependymoma.

BACKGROUND: The role of chemotherapy in recurrent ependymoma is poorly defined. This study was performed to help clarify the benefits of chemotherapy in this setting. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients with advanced ependymoma of the CNS who received chemotherapy in our institution between 1974 and 1993, inclusive. Sixteen consecutive patients were treated with regimens containing either nitrosourea, platinum, or other combinations exclusive of nitrosourea or platinum. No patient received nitrosourea and platinum concurrently. Two methods were used to define response. The first was a direct comparison of radiographic images before and after chemotherapy more than one month apart. A second broader definition of response that employed four other criteria in addition to imaging studies (symptoms, signs, performance status, and neurologic functional status) was also used. RESULTS: Results were as follows (response rate by imaging studies followed by response rate by scoring in parenthesis): Platinum-based chemotherapy resulted in a 67% (83%) response rate with 33% (0%) remaining stable. Nitrosourea-based regimens resulted in a 25% (60%) response rate with 50% (10%) remaining stable. When combinations other than platinum or nitrosourea were used, 11% (22%) responded and 56% (44%) remained stable. Relative differences in response rates between chemotherapy regimens persisted when the data were analyzed by grade. Median time to progression was 6, 10, and 3 months, respectively. CONCLUSION: Platinum-based chemotherapy regimens appear to result in higher response rates with lower rates of progression than nitrosourea-based regimens. Other regimens that do not include cisplatinum or nitrosourea appear to be even less effective.

Adolescent↗

PubMed1999

Phase II North Central Cancer Treatment Group study of 2-cholorodeoxyadenosine in patients with recurrent glioma.

There is no standard treatment for patients with recurrent gliomas, and their prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has significant activity in many low-grade lymphoproliferative disorders. The authors conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in patients with recurrent gliomas. Patients with a histologically confirmed primary brain tumor with evidence of progression after radiation therapy were eligible. Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on days 1 through 5 every 28 days. For those with a history of prior nitrosourea therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1 through 5. Treatment was continued until progression or a maximum of 12 cycles. Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades were entered in the study. Treatment was well tolerated. Major toxicities were myelosuppression and neurotoxicity. No responses were seen. The authors conclude that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity in patients with recurrent gliomas was established.

Adult↗

PubMed1999

Paclitaxel and G-CSF in previously untreated patients with extensive stage small-cell lung cancer: a phase II study of the North Central Cancer Treatment Group.

Paclitaxel is an antimicrotubule agent that interferes with cell division. It has demonstrated promising single-agent activity against non-small-cell lung cancer. The purpose of this study was to evaluate the therapeutic effectiveness of paclitaxel in previously untreated patients with extensive stage small-cell lung cancer (SCLC). The study was designed as a two-stage phase II trial. All patients who entered received paclitaxel by intravenous infusion at a dose of 250 mg/m2 during 24 hours. Granulocyte colony stimulating factor was also provided to ameliorate neutropenia. Cycles were repeated at 21-day intervals. Patients who achieved a complete response received a maximum of 10 cycles of treatment, whereas those who achieved a partial response/regression continued treatment until progression or undue toxicity developed. Patients who progressed or maintained stable disease for six cycles were crossed over to cisplatin and etoposide. Forty-three patients entered the study and all were evaluable for analysis. Responses were observed in 23 (53%) of the patients. There was no significant difference in the response rates in patients with measurable or evaluable disease (13/23 versus 10/20, p = 0.76). At the time of analysis, 39 patients had progressed with a median time to progression of 95 days, and 39 patients had died with a median survival of 278 days. The 1-year achieved survival rate was 24%. Significant neutropenia (absolute neutrophil count <1,000/microl) occurred in 24 (56%) of the patients, but only 2 patients experienced severe infection (grade > or = 3), and there were no septic deaths. The results indicate that paclitaxel is active against SCLC. Myelosuppression was the main side effect in this patient population. Response duration was short (median = 3.4 months), which suggests that paclitaxel is not sufficient as a single agent. Further studies of paclitaxel in combination with other agents against SCLC are currently in progress within the North Central Cancer Treatment Group and other cancer treatment groups. Key Words: Paclitaxel-G-CSF-Small-cell lung cancer-North Central Cancer Treatment Group.

Adult↗

PubMed1999

Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma.

PURPOSE: Because small-cell lung cancer is a rapidly proliferating tumor, it was hypothesized that it may be more responsive to thoracic irradiation (TI) given twice-daily than once-daily. This hypothesis was tested in a phase III trial. PATIENTS AND METHODS: Patients with limited-stage small-cell lung cancer were entered onto a phase III trial, and all patients initially received three cycles of etoposide (130 mg/m(2) x 3) and cisplatin (30 mg/m(2) x 3). Subsequently, patients who did not have progression to a distant site (other than brain) were randomized to twice-daily thoracic irradiation (TDTI) versus once-daily thoracic irradiation (ODTI) given concomitantly with two additional cycles of etoposide (100 mg/m(2) x 3) and cisplatin (30 mg/m(2) x 3). The irradiation doses were TDTI, 48 Gy in 32 fractions, with a 2.5-week break after the initial 24 Gy, and ODTI, 50.4 Gy in 28 fractions. After thoracic irradiation, the patients received a sixth cycle of etoposide/cisplatin, followed by prophylactic cranial irradiation (30 Gy/15 fractions) if they had a complete response. RESULTS: Of 311 assessable patients enrolled in the trial, 262 underwent randomization to TDTI or ODTI. There were no differences between the two treatments with respect to local-only progression rates, overall progression rates, or overall survival. The patients who received TDTI had greater esophagitis (> or = grade 3) than those who received ODTI (12.3% v 5.3%; P =.05). Although patients received thoracic irradiation encompassing the postchemotherapy volumes, only seven of 90 local failures were out of the portal of irradiation. CONCLUSION: When TI is delayed until the fourth cycle of chemotherapy, TDTI does not result in improvement in local control or survival compared with ODTI.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Current guidelines for the management of small cell lung cancer.

Small cell lung cancer (SCLC) accounts for 20% to 25% of cases of bronchogenic carcinoma and results in pronounced morbidity and mortality in the United States. More than 90% of cases of SCLC are caused by cigarette smoking. Common pulmonary manifestations are dyspnea, persistent cough, hemoptysis, and postobstructive pneumonia. At the time of diagnosis, patients usually have extensive disease. To date, therapeutic approaches have made only modest advances in outcome. Combined modality approaches, such as radiotherapy administered concomitantly with the initiation of chemotherapy, induction chemotherapy followed by radiotherapy administered during the subsequent courses of chemotherapy, sequential chemotherapy and radiotherapy, and courses of radiotherapy split between cycles of chemotherapy, are important for improving survival in patients with SCLC.

Carcinoma, Small Cell↗

PubMed1999

Alpha1-antitrypsin deficiency allele carriers among lung cancer patients.

Lung cancer (LC) and chronic obstructive pulmonary lung diseases (COPDs; including emphysema and chronic bronchitis) share a common etiology. Despite the known associations of alpha1-antitrypsin deficiency (alpha1AD) with COPD and COPD with LC, few studies examined the association of alpha1AD alleles and LC. We hypothesize that heterozygous individuals who carry a deficient allele of the alpha1AD gene Pi (protease inhibitor locus) are at an increased risk of developing LC. The Pi locus is highly polymorphic with >70 variants reported. There are at least 10 alleles associated with deficiency in alpha1-antitrypsin. Using an exact binomial test, we compared the alpha1AD carrier rate in 260 newly diagnosed Mayo Clinic LC patients to the reported carrier rate in Caucasians in the United States (7%). alpha1AD carrier status, determined by isoelectric focusing assay, was examined with respect to the history of cigarette smoking, COPD, and histological types. Thirty-two of the 260 patients (12.3%; 95% confidence interval, 8.6-16.9%) carried an alpha1AD allele, which was significantly higher than expected (P = 0.002). Twenty-four of the 32 carriers had allele S, 6 had allele Z, and 2 had allele I. Patients who never smoked cigarettes were three times more likely to carry a deficient allele (20.6%; P = 0.008), although smokers had a higher carrier rate (11.1%; P = 0.025) when compared with the 7% rate. Patients with squamous cell or bronchoalveolar carcinoma had a significantly higher carrier rate than expected (15.9% and 23.8%, P < or = 0.01, respectively). Our preliminary findings suggest that individuals who carry an alpha1AD allele may have an increased risk for developing LC, specifically squamous cell or bronchoalveolar carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1998

Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma.

PURPOSE: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. METHODS AND MATERIALS: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m2 days 1-3, cisplatin 30 mg/m2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m2 every 8 weeks x 4 cycles was given after radiation therapy. RESULTS: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m2 days 1-3, cisplatin 20 mg/m2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 microg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean +/- SD 2 hr and 6 hr plasma concentrations were 0.92 +/- 0.43 microg/ml and 0.36 +/- 0.12 microg/ml, respectively. Estimated duration of exposure to >0.1 microg/ml etoposide was 10-17 hr. CONCLUSIONS: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.

Adult↗

PubMed1998

Phase II trial of topotecan for the treatment of mesothelioma.

The North Central Cancer Treatment Group designed a phase II trial to assess the efficacy and toxicity of topotecan in patients with unresectable malignant pleural mesothelioma. Twenty-two previously untreated patients with unresectable pleural mesothelioma and good performance status (Eastern Cooperative Oncology Group performance status 0, 1, or 2) were enrolled on this trial from October 1993 through July 1994. Nineteen men and three women, median age 66 years (range, 44-78 years), were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days at 3-week intervals until toxicity, progression of disease, or a patient decided to discontinue treatment. There were seven patients with measurable disease and 15 with evaluable disease; all were assessable for response and toxicity. A total of 113 cycles of treatment were given, for a median of three cycles (range, 1-26 cycles). Myelosuppression was the most frequent toxicity. Eighteen of 21 patients (86%) experienced grade 3 or 4 neutropenia during the initial treatment cycle. The median neutrophil nadir was 0.5 x 10(3)/microl (range, 0.1-1.6 x 10(3)/microl), and the median platelet nadir was 127 x 10(3)/microl (range, 18-460 x 10(3)/microl). Other toxicities more than grade 2 included malaise (two patients), and anorexia, infection, fever, pulmonary, and cardiac in one patient each. There were no objective responses, and 18 patients had stable disease for a median of 74 days. The median survival for all patients was 230 days, with 23% alive at 1 year. Topotecan as administered in this trial is reasonably well tolerated; however, the response rate was insufficient to warrant additional study in pleural mesothelioma.

Adult↗

PubMed1997

The impact of surgical adjuvant thoracic radiation therapy for patients with nonsmall cell lung carcinoma with ipsilateral mediastinal lymph node involvement.

BACKGROUND: Previous nonsmall cell lung carcinoma studies have shown that patients with ipsilateral mediastinal (N2) lymph node involvement who underwent surgical resection have a greater local recurrence rate than those with less lymph node involvement (N0, N1). Therefore, it was hypothesized that complete surgical clearance of subclinical lymph node disease is difficult in N2 patients and that adjuvant postoperative thoracic radiotherapy (TRT) may be beneficial. METHODS: A retrospective review was performed to determine the local recurrence and survival rates for patients with N2 disease undergoing complete surgical resection with or without adjuvant TRT. Between 1987 and 1993 at the Mayo Clinic, 224 patients underwent complete resection of N2 nonsmall cell lung carcinoma. More than one mediastinal lymph node station was sampled in 98% of patients; 39% then received adjuvant TRT (median dose, 50.4 grays). RESULTS: The median follow-up time was 3.5 years for the patients who were alive at the time of the analysis. The surgery alone versus surgery plus TRT groups were well balanced with respect to gender, age, histology, tumor grade, number of mediastinal lymph node stations dissected or involved, and involved N1 lymph node number. There were slightly more patients with right lower lobe lesions (compared with other lobes), patients with multiple lobe involvement, and patients with only one N2 lymph node involved in the surgery alone group. After treatment with surgery alone, the actuarial 4-year local recurrence rate was 60%, compared with 17% for treatment with adjuvant TRT (P < 0.0001). The actuarial 4-year survival rate was 22% for treatment with surgery alone, compared with 43% for treatment with adjuvant TRT (P = 0.005). On multivariate analysis, the addition of TRT (P = 0.0001), absence of superior mediastinal lymph node involvement (P = 0.005), and fewer N1 lymph nodes involved (P = 0.02) were independently associated with improved survival rate. CONCLUSIONS: This study, which to the authors' knowledge is the largest evaluating adjuvant TRT in N2 nonsmall cell lung carcinoma, suggests that adjuvant TRT may improve local control and survival.

Carcinoma, Non-Small-Cell Lung↗