Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress.
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PMID:[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. 17 37

VP 16-213, the new semisynthetic epipodophyllotoxin, was tested for activity and toxicity in two small pilot series of 24 mainly untreated patients with anaplastic, predominantly small-cell lung cancer. It was given in combination with cyclophosphamide or adriamycin. Among 10 evaluable patients receiving VP-16 + cyclophosphamide (5 orally, 5 intravenously) only 1 good partial remission and 4 partial remissions (less than 50%) were achieved. Toxicity was minimal. In 14 patients on VP-16 and adriamycin, remission was complete in 2, good partial in 5 and lesser partial in 2. The hematological toxicity of the second combination was marked. Severe granulocytopenia required reverse isolation of most patients for periods of up to 2 weeks. The response rate for VP-16 + adriamycin was better than for VP-16 + cyclophosphamide, but lower than expected. Possible explanations are given.
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PMID:[Experiences with VP-16 in combination with cyclophosphamide or adriamycin in the anaplastic, predominantly small cell bronchogenic carcinoma]. 46 56

The objectives of this study were to define the pharmacodynamics of etoposide and to develop potentially useful models (1) to estimate the plasma clearance using a limited number of samples and (2) to describe the relationship between clearance and the dose-limiting toxicity. A total of 17 patients with extensive-stage small-cell lung cancer were treated with 150 mg/m2 etoposide daily for 3 consecutive days and with 100 mg/m2 cisplatin on day 3 only. Both drugs were given intravenously over 1 h. Treatment was repeated every 21 days for up to six courses. All patients were newly diagnosed (no previous chemotherapy or irradiation) and had a performance status of 0-2. Six patients achieved a complete response as confirmed by repeat bronchoscopy and five patients showed a partial response, for an overall objective response rate of 65% (95% confidence interval, 38%-87%). The median survival was 8 months (range, 1-24+ months). The dose-limiting toxicity was neutropenia. Etoposide pharmacokinetics were measured during the first course and determinations were repeated during courses 3 or 4 and 6. Complete blood counts were obtained weekly. Correlations for etoposide clearance and hematologic toxicities were evaluated for 17 initial courses and for an overall number of 33 courses. Pharmacodynamic correlations were significant for graded hematologic toxicities, as well as nadirs of leukocytes, neutrophils, and platelets for the initial courses and for all courses. To reduce the requirement for numerous blood samples, a limited sampling model was developed to estimate the area under the concentration versus time curve (AUC) with the following equation: AUC = 15.45 + 3.86 x C2 + 7.10 x C4, where C2 and C4 represent the etoposide concentrations at 2 and 4 h, respectively. The total plasma clearance was calculated as the dose divided by the AUC; correlations with toxicity were better for clearance expressed in milliliters per minute than for that expressed in milliliters per minute per square meter of body surface area. The absolute neutrophil count at the nadir (ANCn) can be estimated by the following pharmacodynamic model, which is based on 33 courses: ANCn = -0.399 + 0.024 x Ecl, where Ecl represents the etoposide clearance expressed in milliliters per minute. Further studies are necessary to validate both models prospectively.
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PMID:Pharmacodynamics of three daily infusions of etoposide in patients with extensive-stage small-cell lung cancer. 133 71

Twenty patients with stage IIIA-IIIB non-small-cell lung cancer were treated with cisplatin, epirubicin and VP-16 (PEV) neoadjuvant chemotherapy (CDDP, 70 mg/m2, i.v., d 1; EDX, 60 mg/m2, i.v., d 1; VP-16, 100 mg/m2, i.v., d 1-2-3; every 3 weeks). A partial response was obtained in 11 cases (55%), stable disease in 3 cases (15%), and progressive disease in 6 cases (30%). After chemotherapy, 8 (40%) patients, all achieving a partial response, were elegible for surgery: 5 (25%) had a complete resection (4 IIIA and 1 IIIB) and 3 (15%) an incomplete resection. The treatment was well tolerated. These data show that PEV is an active regimen for neoadjuvant chemotherapy in NSCLC and recommend this therapeutic approach for stage IIIA patients.
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PMID:Neoadjuvant chemotherapy with cisplatin, epirubicin and VP-16 for stage IIIA-IIIB non-small-cell lung cancer: a pilot study. 133 3

Etoposide, a podophyllotoxin derivative, has demonstrated antitumor efficacy in a number of human malignancies, including lymphomas, germinal tumors, and lung cancer (especially small cell). Etoposide's antineoplastic activity is achieved through DNA strand breakage, which likely results from the formation of a complex involving drug, DNA, and the DNA unwinding enzyme, topoisomerase II. The drug's steady state volume of distribution ranges from 5 to 17 L/m2, and it is highly bound to plasma protein with an average free plasma fraction of 6%. A number of etoposide metabolites have been confirmed or postulated. Several cell lines have been shown to acquire resistance to etoposide through membrane transport changes. Considerable intrapatient variability exists in pharmacokinetic parameters following intravenous (IV) and oral dosing. Approximately 30% to 40% of unchanged IV drug is excreted in the urine, whereas biliary excretion appears a minor route of drug elimination. The bioavailability of oral etoposide averages 50%, although wide variability exists both among and within different patients. Bioavailability decreases as the dose of oral etoposide is increased. Several recent studies have attempted to correlate etoposide plasma concentrations with toxicity (primarily myelosuppression) in hopes of using this information to optimize drug dosing.
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PMID:Etoposide pharmacology. 149 25

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.
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PMID:[Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma]. 149 52

Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage.
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PMID:A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. 164 92

A randomized study comparing teniposide (VM-26) and etoposide (VP-16) was performed to investigate whether there are any differences in the activity and toxicity of these two analogs in small-cell lung cancer (SCLC). Only previously untreated patients with SCLC were included; 46 and 48 patients receiving VP-16 and VM-26, respectively, are assessable for response. There were no differences between the two groups with respect to extent of disease, median age, and performance status (PS). The initial doses were for both compounds 70 mg/m2 intravenously (IV) daily for 5 days every 3 weeks. After inclusion of 25 patients in the study, the doses were increased to 80 mg/m2 for VM-26 and 90 mg/m2 for VP-16 because of differences in toxicity. VM-26 caused more hematologic toxicity than VP-16 throughout the study. The overall responses (complete response [CR] plus partial response [PR]) were 65% for VP-16 and 71% for VM-26, with CR occurring in 24% and 23%, respectively, for the two compounds. Median survival was 8.5 months for VP-16-treated patients versus 11.3 months for VM-26-treated patients (P = .58). It is concluded that both VP-16 and VM-26 are highly active single agents in SCLC.
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PMID:Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study. 165 94

Using the double agar layer method of human tumor clonogenic assay, the anticancer effect of different combinations of anticancer drugs and interferons was tested on 3 lung cancer cell lines, PC-13, PC-14, and Calu-1. The anticancer drugs and the concentrations used in this study were cisplatin (1.0 microgram/mL), adriamycin (1.0 microgram/mL), mitomycin C (0.2 microgram/mL), VP-16 (5.0 micrograms/mL) and 5-FU (5.0 micrograms/mL). Three kinds of interferon, alpha, beta and gamma in 5,000 units/mL, were tested in combination or in sequence with other anticancer drugs on lung cancer cell lines. The results demonstrate an enhanced anticancer effect on PC-14 only with sequential or simultaneous combination of VP-16 with alpha, beta and gamma interferons; and on Calu-1, only with sequential use of adriamycin and beta-interferon. Our results indicate that there is no unique way of combining anticancer drugs and interferons which can obtain an enhanced anticancer effect on all lung cancer cell lines. The best combination of interferon and anticancer drugs seems to be influenced by the biological characteristics of the cancer cells.
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PMID:[Effect of combinations of anticancer drugs with interferons on human lung cancer cell lines evaluated by human tumor clonogenic assay]. 172 Jan 64

To noninvasively study positional effects on superior vena caval configuration in humans, endoscopic ultrasonography was performed in 34 subjects including 20 with lung cancer, 5 with esophageal cancer and 9 with other diseases. None of the these subjects had cardiovascular involvement or respiratory dysfunction. A fiberoptic esophagoscope equipped with a 7.5 MHz linear array ultrasonic transducer at its tip (EPE-703, Toshiba-Machida) was used for the study. The actual movement of the superior vena cava (SVC) was clearly observed at the hilar level in all cases. During the cardiac cycle the anteroposterior diameter of the SVC was observed to reach a maximum at the atrial systole and reached a minimum at the late ventricular systole. With respiration, the SVC increased in diameter during inspiration and decreased during expiration. Moreover M and B mode figures of the SVC wall were recorded in left (LLD) and right decubitus (RLD) and supine position (SUP) in 34 subjects. On quiet ventilation of FRC level the diameter of the SVC was unchanged. Both the maximal and minimal diameters of the SVC, which were corrected for body surface area (BSA), were 11.3 +/- 0.3 (mean +/- SEM) mm/m2 and 9.8 +/- 0.3 mm/m2 in right lateral decubitus position, 9.4 +/- 0.3 and 7.9 +/- 0.3 in the supine position, 8.5 +/- 0.3 and 7.1 +/- 0.3 in the left lateral decubitus position, respectively. The size of the SVC was the greatest in the right lateral decubitus position and was the smallest in left lateral decubitus position (p less than 0.01, multiple comparison). It was suggested that the geometry of the SVC is influenced by thoracic pressure and gravity and that it behaves very similarly to pulmonary vascular vessels as a collapsible tube.
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PMID:[Dynamic changes in superior vena caval configuration based on posture]. 175 32


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