Small cell lung cancer and chemotherapy

We report a case of a spontaneous pneumothorax in association with a major burn. The pneumothorax remained undetected for 4 days and the patient underwent a 2 h aeromedical transfer which could potentially have been hazardous. We strongly recommend that arterial blood gas analysis is performed before air transport of moderate or severely burned patients. If blood gases are abnormal a chest X-ray should also be performed. In practice a strong case can be made for routinely obtaining a chest X-ray in these patients. In-flight monitoring should include pulse oximetry.     

Staging of the patient with small cell lung cancer

This chapter addresses primary and secondary manufacturing, exposure monitoring, engineering controls, and personal protective equipment in the pharmaceutical industry. Trends affecting industrial hygiene also are examined.     

Efficacy of neoadjuvant chemotherapy in primary non-small cell lung cancer

PURPOSE: To examine the changes in ciliary body thickness after topical application of pilocarpine, cyclopentolate hydrochloride, and PhXA41, a prostaglandin F2alpha analog. METHOD: We used high-frequency Humphrey UBM840 ultrasound biomicroscope to examine 36 healthy young Japanese subjects. RESULTS: The mean ciliary body thickness increased from 0.67 +/- 0.07 mm to 0.073 +/- 0.08 mm (P < .01) after application of 2% pilocarpine; 1% cyclopentolate hydrochloride and 0.005% PhXA41 decreased the mean ciliary body thickness from 0.75 +/- 0.07 mm to 0.69 +/- 0.05 mm (P < .05) and from 0.78 +/- 0.06 mm to 0.75 +/- 0.06 mm (P < .01), respectively. CONCLUSIONS: Our ultrasound study clearly indicates that pilocarpine increased comparative thickness of the ciliary body by 8.3%, whereas PhXA41 decreased comparative thickness by 3.3% in a manner similar to cyclopentolate hydrochloride.     

Hyperfractionated radiotherapy combined with simultaneous chemotherapy in inoperable non-small cell lung cancer: a pilot study

Between March 1992 and February 1993, hyperfractionated radiotherapy (HRT) (1.2 Gy.fraction-1, twice a day, total dosage of 69.6 Gy) and simultaneous cisplatin (70 mg.m-2, 3rd and 23rd days of HRT) and etoposide (70 mg.m-2, 1-3rd and 20-23rd days of HRT) were applied to 27 patients with inoperable non-small cell lung cancer (NSCLC). Their Karnofsky performance statuses were 70-90%, and mean age was 52 (36-63). Two cases were stage II (one of the patients refused the operation and the other was medically inoperable because of insufficient ventilation), eight were stage IIIA and 17 were stage IIIB. No severe life-threatening grade IV acute toxicity findings were observed. Generally, acute side-effects were transient and did not require discontinuation of treatment. Tumour responses were as follows: complete response in six cases (23%); partial response in 19 cases (70%); and stable disease in two (7%). When complete response rates were compared according to stage, histological type, age group and weight loss, no statistically significant difference was found. Median overall and disease-free survival times were 14 months (95% confidence interval) (95% CI) 11-17 months and 10 months (95% CI 7-13 months), respectively. Twelve and 24 months overall and disease-free survival rates were 56 and 30%, and 36 and 24% respectively. No statistically significant difference was found in overall survival rates among epidermoid and nonepidermoid types, while the difference in disease-free survival was statistically significant. The acute and late complications of our HRT and simultaneous chemotherapy protocol were tolerable and the survival rates were encouraging.     

Alternating chemotherapy in advanced non-small cell lung cancer: a phase II study

Fifty-three patients with advanced non-small cell lung cancer (NSCLC) were treated with alternating two-drug schedules cisplatin/vindesine and ifosfamide/mitomycin. Objective response (complete and partial response) was obtained in 31% (confidence limits 18.6-44%) of patients. The median duration of response was 26 weeks. The median survival was 25 weeks, with 24% of patients alive at 1 year. The toxicity was acceptable. The still poor antitumor activity of the chemotherapy schedules used and the lack of non-cross-resistance are factors that could explain the low antitumor activity of alternating chemotherapy.     

Combination chemotherapy studies with gemcitabine and etoposide in non-small cell lung and ovarian cancer cell lines

Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and etoposide (4'-demethylepipodo-phyllo-toxin-9-4,6-O-ethylidene-beta-D-g lucopyranoside, VP-16) are antineoplastic agents with clinical activity against various types of solid tumors. Because of the low toxicity profile of dFdC and the differences in mechanisms of cytotoxicity, combinations of both drugs were studied in vitro. For this purpose, we used the human ovarian cancer cell line A2780, its cis-diammine-dichloroplatinum-resistant and VP-16 cross-resistant variant ADDP, and two non-small cell lung cancer cell lines, Lewis Lung (LL, murine) and H322 (human). The interaction between the drugs was determined with the multiple drug effect analysis (fixed molar ratio) and with a variable drug ratio. In the LL cell line, the combination of dFdC and VP-16 at a constant molar ratio (dFdC:VP-16 = 1:4 or 1:0.125 after 4- or 24-hr exposure, respectively) was synergistic (combination index [CI], calculated at 50% growth inhibition = 0.7 and 0.8, respectively; CI <1 indicating synergism). After 24- and 72-hr exposure to both drugs at a constant ratio, additivity was found in the A2780, ADDP, and H322 cell lines (dFdC:VP-16 = 1:500 for both exposure times in these cell lines). When cells were exposed to a combination of dFdC and VP-16 for 24 or 72 hr, with VP-16 at its IC25 and dFdC in a concentration range, additivity was found in both the LL and H322 cells; synergism was observed in the A2780 and ADDP cells, which are the least sensitive to VP-16. Schedule dependency was found in the LL cell line; when cells were exposed to dFdC 4 hr prior to VP-16 (constant molar ratio, total exposure 24 hr), synergism was found (CI = 0.5), whereas additivity was found when cells were exposed to VP-16 prior to dFdC (CI = 1.6). The mechanism of interaction between the drugs was studied in more detail in the LL cell line; dFdCTP accumulation was 1.2-fold enhanced by co-incubation with VP-16, and was even more pronounced (1.4-fold) when cells were exposed to VP-16 prior to dFdC. dCTP levels were decreased by VP-16 alone as well as by the combination of both compounds, which may favor phosphorylation of dFdC, thereby increasing dFdCTP accumulation. DNA strand break (DSB) formation was increased for exposure to both compounds together compared to exposure to each compound separately, this effect being most pronounced when cells were exposed to VP-16 prior to dFdC (38% and 0% DSB for dFdC and VP-16 alone, respectively and 97% DSB for the combination). The potentiation in DSB formation might be a result of the inhibition of DNA repair by dFdC. Provided the right schedule is used, VP-16 is certainly a compound eligible for combination with dFdC.     

Disease-free survival in a patient with squamous cell lung carcinoma following complete response with the combination chemotherapy of cisplatin and etoposide

Disease-free survival is reported in a patient with non-small cell lung carcinoma successfully treated with the combination chemotherapy of cisplatin and etoposide (CDDP-ETOP). An 80-year-old woman was diagnosed as having squamous cell carcinoma of the lung with bone metastasis. Chest X-ray showed a tumor (64 x 68 mm in size) in the S1/4 segment of the right lobe, and CT scan revealed no apparent metastasis of hilar lymphnode. In March 1989, the patient achieved a complete response (CR) after two courses of CDDP-ETOP therapy, followed by ETOP(100mg) every two weeks and daily UFT (400 mg) for 10 months. Subsequently, a single course of CDDP-ETOP was administered as a consolidation therapy. The patient is alive with no evidence of recurrent disease for 3 years and half after achieving CR.     

Accelerated-interrupted radiation therapy given concurrently with chemotherapy for locally advanced non-small cell lung cancer

PURPOSE: To evaluate the efficacy of multidrug chemotherapy combined with accelerated radiation therapy in the treatment of localized but unresectable non-small cell lung cancer. PATIENTS AND METHODS: Between September 1990 and February 1993, 35 patients with Stage III (15 IIIA & 20 IIIB) non-small cell lung cancer were entered on a protocol using combined accelerated radiation therapy and chemotherapy. Radiation therapy consisted of 55.6 Gy in 30 fractions (1.8 Gy bid for 5 consecutive days given in 3 weeks [total of 15 days], every other week). Chemotherapy consisted of cisplatin (10 mg/m2), vinblastine (4 mg/m2), 6-thioguanine (40 mg bid), and 5-fluorouracil (400 mg/m2 as continuous infusion) given concomitantly with radiation therapy. Approximately 3 weeks following completion of radiation therapy, two cycles of consolidation chemotherapy were given, consisting of two doses of cisplatin (120 mg/m2) 4 weeks apart and six doses of vinblastine (4 mg/m2) given on two consecutive days every other week for 3 weeks. RESULTS: Six patients were still alive at last follow-up; for them the median follow-up time is 47 months (range, 39-55.8). The median survival time is 17.5 months. The 1-, 2-, 3- and 4.5-year survival rates are 69%, 37%, 20% and 17%, respectively. Overall response rate is 63%, with 51.5% partial response and 11.5% complete response rates. Esophagitis occurred as follows: Grade 4 = 0, Grade 3 = 1, Grade 2 = 6, and Grade 1 = 13. No patient developed Grade 3 or 4 acute respiratory toxicity. Significant hematologic toxicity occurred as follows: 37% Grade 3 and 31% Grade 4 leukopenia. Radiation pneumonitis occurred in two patients. DISCUSSION: The regimen tested in this protocol appears to be very well tolerated with minimal pulmonary or esophageal toxicity. This, coupled with the shortened course of radiation therapy and the ability to deliver the combined radiation and chemotherapy portion of the treatment on an outpatient basis most of the time, has made multi-modality treatment for this malignancy much easier and more convenient for patients. In addition, the favorable survival in this group of patients with locally advanced disease is very encouraging and warrants further study.     

Local treatment with tumor necrosis factor alpha in a patient with lung cancer

Tumor Necrosis Factor alfa (TNFa) is a cytokine with cytolytic and cytotoxic properties. First clinical trials in which TNF was administered parenterally date back to early 70-ties. Soon it was noticed that when administered strictly to the tumor mass TNF exhibits high anti-tumor efficacy, exemplified by total or at least substantial regression of the tumor mass while producing minor and controllable symptoms. In this paper the case of local administration of the recombinant TNFa directly into the tumor mass constricting the bronchus was presented.     

Myositis associated with interleukin-2 therapy in a patient with metastatic renal cell carcinoma

BACKGROUND: Interleukin-2 (IL-2) has been used successfully in the treatment of some patients with metastatic renal cell carcinoma and melanoma, with a partial response rate of 15%-20%. It produces a well documented spectrum of side effects. Autoimmune diseases have been associated with IL-2 immunotherapy and the development of autoimmune thyroiditis may correlate with antitumor clinical response. METHODS: A patient with metastatic renal cell carcinoma is described who developed a polymyositis-like myopathy after an autologous tumor vaccine and IL-2 therapy. RESULTS: The patient had a delayed response for 15 months after developing this previously unreported toxicity. CONCLUSIONS: To the authors' knowledge, this represents the first reported case of necrotizing myositis in association with IL-2 therapy. Subsequent continuous partial response of the advanced malignancy was observed for 15 months. In this case, IL-2 may have broken tolerance to both normal muscle cells and tumor cells.     

Evaluation of the response to chemotherapy in patients affected with small cell lung cancer using discriminant analysis: a preliminary report

This research was carried out at the University Hospital of the University of S?o Paulo and deals with the experiment of papain utilization for visceral irrigation in patients with severe infection. It was observed that seventy two hours after treatment, there was a considerable reduction of purulent secretion, and that the medium time of cicatrization of all lesions was thirty days.     

Costs of care associated with non-small-cell lung cancer in a commercially insured cohort

PURPOSE: To examine the cost of incident cases of non-small-cell lung cancer (NSCLC) in a commercially insured cohort. METHODS: Claims from Virginia Blue Cross and Blue Shield (BCBS) beneficiaries with lung cancer from 1989 to 1991 were merged with records from the Virginia Cancer Registry (VCR). Data from the VCR identified incident cases, stage, and type of cancer at diagnosis. Costs for all medical care included insurance payment, copayments, and deductibles for 2 years after diagnosis or until death. RESULTS: Three hundred forty-nine incident NSCLC patients were evaluated. The mean 2-year cost for each patient after diagnosis or until death was $47,941 (95% confidence interval, $43,758 to $52,124). Total average costs and hospital days were significantly lower for local disease ($37,514, 21.2 days), but were similar for regional ($52,797, 30.0 days) and distant ($49,382, 33.0 days) disease. Hospital days accounted for 48% and hospital-based claims for 70% of costs. Initial treatments, which included radiation, unadjusted for stage, had the lowest survival rates and the highest costs, and were associated with the most hospital days. Initial stage, race, gender, and age were not predictors of total 2-year costs. The independent predictors of total 2-year costs were type of treatment: any radiation therapy, any surgery, or any chemotherapy (all, P < .001). Inpatient hospital days was only a modest predictor of costs after adjusting for type of treatment. Patients who survived less than 1 year spent 30.5 days in hospital and had an average cost of $47,280. CONCLUSION: The direct health care costs of younger NSCLC patients care are substantial. These results should serve as a benchmark for future comparisons as the United States market shifts to managed care.     

Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews

OBJECTIVE: To determine how patients with lung cancer value the trade off between the survival benefit of chemotherapy and its toxicities. DESIGN: Scripted interviews that included three hypothetical scenarios. Each scenario described the same patient with metastatic non-small cell lung cancer with an expected survival of 4 months without treatment. Subjects were asked to indicate the minimum survival benefit required to accept the side effects of chemotherapy in the first two scenarios (mild toxicity and severe toxicity). In the third scenario, subjects were asked to choose between chemotherapy and supportive care when the benefit of chemotherapy was either to prolong life by 3 months or to palliate symptoms. SUBJECTS: 81 patients previously treated with cis-platinum based chemotherapy for advanced non-small cell lung cancer. MAIN OUTCOME MEASURE: Survival threshold for accepting chemotherapy. RESULTS: The minimum survival threshold for accepting the toxicity of chemotherapy varied widely in patients. Several patients would accept chemotherapy for a survival benefit of 1 week, while others would not choose chemotherapy even for a survival benefit of 24 months. The median survival threshold for accepting chemotherapy was 4.5 months for mild toxicity and 9 months for severe toxicity. When given the choice between supportive care and chemotherapy only 18 (22%) patients chose chemotherapy for a survival benefit of 3 months; 55 (68%) patients chose chemotherapy if it substantially reduced symptoms without prolonging life. CONCLUSIONS: Patients' willingness to accept chemotherapy for the treatment of metastatic lung cancer varies widely. Many would not choose chemotherapy for its likely survival benefit of 3 months but would if it improved quality of life. The conflict between these patients' preferences and the care they previously received has several explanations, one being that some patients had not received the treatment they would have chosen had they been fully informed.