Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and pathological entity other than small cell carcinoma of the lung. We present a case with EPSCC, with neurologic impairment due to brain metastases at initial diagnosis, which showed a complete response to combination chemotherapy. A 55-year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in the right cervical region. The diagnosis of small cell carcinoma was entertained with immunohistopathologic and light microscopic findings. During the period of investigation the tumor showed rapid progression and the patient had neurologic dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT showed supratentorial multiple cranial metastases and peritumoral oedema. Since the patient refused radiotherapy, combination chemotherapy was started (Etoposide 100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast response to the chemotherapy was observed with rapid disappearance of the cervical mass. Following six cycles of the chemotherapy the patient recovered fully and all the lesions disappeared with CT.
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PMID:Successful treatment of cranial metastases of extrapulmonary small cell carcinoma with chemotherapy alone. 964 34

A 32-year-old man presented with a swelling of the left testis, for which he underwent high inguinal orchiectomy. Histopathological examination of the specimen revealed teratocarcinoma. Further evaluation revealed no metastasis (stage I), and he was followed-up by monthly examination without prophylactic chemotherapy (surveillance). Thirteen months after orchiectomy, AFP and hCG-beta were elevated at 133.8 ng/ml and 0.8 ng/ml respectively. Abdominal CT scan revealed para-aortic masses of recurrent tumor. Although the AFP and hCG-beta levels markedly declined after five courses of COMPE (CDDP, VCR, MTX, PEP, Etoposide) chemotherapy, the retroperitoneal masses had further enlarged and had undergone cystic change. Excision of the residual tumors was performed, and microscopic examination of specimens revealed mature teratoma without malignant components. The diagnosis of the growing teratoma syndrome was therefore made. The growing teratoma syndrome occurs in nonseminomatous testicular germ cell tumors following chemotherapy and is characterized by enlargement of metastatic lesions with normal tumor marker levels. Total surgical resection of the mass yields good results, and tumor is unresponsive to chemotherapy. Early recognition of this syndrome is important for successful treatment.
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PMID:[The growing teratoma syndrome: report of a case]. 978 Jun 59

This was a pharmacological companion study to a randomized Phase III trial comparing 21-day oral versus 3-day i.v. etoposide in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer. Etoposide plasma concentrations were measured in patients randomized to the 21-day schedule and correlated with toxicity and tumor response. Patients were treated with etoposide (50 mg/m2/day) orally for 21 days and cisplatin (33 mg/m2/day) i.v. for 3 consecutive days every 28 days for 6 courses. Plasma samples before the daily etoposide dose (trough concentrations) and complete blood counts were obtained weekly during treatment. The average of three etoposide concentrations (EC) per course was calculated. Of 158 patients registered to this schedule of the study, 150 were eligible. In 106 patients, etoposide samples were obtained at least in the first course in which the mean EC was 0.39 microgram/ml (SD = 0.29). In 102 patients (missing albumin values in 4 of 106 patients), the concentration of etoposide not bound to protein (Efree) was estimated based on the following equation: percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4. Regression analysis revealed that increasing age was correlated with higher EC (r = 0.27; two-tailed P < 0.01) and Efree (r = 0.31; two-tailed P < 0.01). Higher EC and Efree values were associated with lower WBC counts and absolute neutrophil counts after the first treatment course in 83 patients with nadir counts. Using multiple linear regression, a pharmacodynamic model was developed that included EC or Efree, age, and alkaline phosphatase. An interaction with bone marrow results at diagnosis was found, indicating a sharper decline in nadir counts with increasing EC or Efree when the marrow was involved with small cell lung cancer. This model explained 29% of the variation for WBC nadirs (P < 0.001) and 31% of the variation for absolute neutrophil count nadirs (P < 0. 001). Neither EC nor Efree showed a significant correlation with tumor response. A pharmacokinetic relationship between EC or Efree and age was found. A pharmacodynamic model could be developed for toxicity but not for tumor response.
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PMID:Pharmacology of 21-day oral etoposide given in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer: a cancer and leukemia group B study (CALGB 9062). 981 41

Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy, we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity. Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil, as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3] i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia. The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.
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PMID:Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma. 981 97

Superselective intraarterial infusion of etoposide and cisplatin was performed in 2 patients with recurrent malignant lymphoma which had progressed after operation, radiotherapy and chemotherapy with various anticancer agents. The tip of a microcatheter (Tracker-18) was placed in the left posterior cerebral artery in the first patient with the recurrent tumor located in the left occipital lobe and at the basilar top in the second patient with the recurrent tumor extending from the right thalamus to the pons. Etoposide (60 mg) and Cisplatin (60 mg) were each infused for 1 hour safely with a combination of intermittent infusion of nicardipine and papaverine chloride. The tumor disappeared completely after 2 courses of intraarterial chemotherapy in the first patient and after 1 course in the second patient. Intraarterial chemotherapy using a combination of etoposide and cisplatin was performed safely and showed good results.
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PMID:[Intraarterial chemotherapy using a combination of etoposide and cisplatin for recurrent malignant lymphoma]. 983 20

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies".
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PMID:[Late toxicity after chemotherapy of malignant testicular tumors]. 988 93

Six metastatic breast cancer patients, including one brain metastasis, one lung metastasis, three local recurrences and one bone metastasis, underwent multidrug chemotherapy with CBDCA, Etoposide (ETP) and Epirubicin (EPI). Each patient received two courses of PBSC mobilization chemotherapies and subsequently received high-dose chemotherapies for at least two courses. CBDCA AUC 4, ETP 300 mg/m2 and EPI 40 mg/m2 were administered intravenously as a PBSC mobilization chemotherapy, and high-dose chemotherapies were performed under the regimen of CBDCA AUC 8, ETP 900 mg/m2 and EPI 60 mg/m2. Severe bone marrow suppression due to high-dose chemotherapies was off sct by autologous peripheral blood stem cell transplantation (PBSCT). The PBSC mobilization chemotherapies resulted in one CR, three PR, one NC and one PD in the six patients. The PD patient died before high-dose chemotherapy. Consequently, the remaining five patients received the high-dose chemotherapies, which achieved three CR, one PR and one PD in the five patients. The response rate of high-dose chemotherapy was 80% (4/5 cases). In overall outcome, three patients have continued 16, 12 and 10 months tumor-free survival, and three patients died of cancer progression. High-dose chemotherapy with CBDCA, ETP and EPI has led to increased CR rates in metastatic breast cancer, and such therapy has desirable effect on the patient's prognosis.
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PMID:[CBDCA, etoposide and epirubicin high-dose combination chemotherapy supported by peripheral blood stem cell transplantation (PBSCT) in metastatic breast cancer]. 998 2

Etoposide (VP16), a widely used anticancer drug, is a topoisomerase II inhibitor. A number of studies have highlighted a correlation between hematologic toxicity and pharmacokinetic or physiological parameters. Other studies have also suggested that the anti-tumor response could be related to the plasma etoposide concentration. Therefore, it would seem of interest to individualize VP16 dose regimens on the basis of pharmacokinetic parameters. The aim of this study was to develop and validate a limited-sampling strategy allowing VP16 pharmacokinetic evaluation with minimal disturbance to the patient. A total of 34 patients (54 kinetics) received VP16 at various dose regimens, with doses ranging between 30 and 200 mg and infusion times varying between 0.5 and 2 h. The statistical characteristics of the pharmacokinetic parameters were assessed from the first courses of treatment performed in 23/34 patients; then the following three-sample protocol was designed: the end of the infusion and 5 and 24 h after the start of the infusion. For validation of the model the main pharmacokinetic parameters (clearance, half-lives, volume of distribution) were estimated in the 11 remaining patients by maximum-likelihood estimation (ML) and by Bayesian estimation (BE) using the three sampling times designed. Statistical comparison showed a good concordance between ML and BE estimates (the bias for clearance was -1.72%). The limited-sampling strategy presented herein can thus be used for accurate estimation of VP16 pharmacokinetic parameters.
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PMID:A limited-sampling strategy for estimation of etoposide pharmacokinetics in cancer patients. 1007 83

Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIalpha (topo IIalpha) gene expression. Etoposide-resistant MDA-VP human breast cancer cells express lower amounts of enzymatically active and drug-sensitive topo IIalpha than do MDA parent cells, suggesting that the low level of topo IIalpha is the mechanism of resistance. To determine whether transfer of a normal topo IIalpha gene into MDA-VP cells can increase topo IIalpha gene expression, topo IIalpha protein production, and cell sensitivity to etoposide, a recombinant adenovirus, Ad-hTopoIIalpha, containing the human topo IIalpha gene, was constructed. The shuttle vector pAvCvSv-hTopIIalpha was constructed and co-transfected with the pBHG10 packaging vector into 293 cells. Infectious recombinant adenovirus plaques were isolated and purified. Presence of the topo IIalpha gene was confirmed by PCR and restriction enzyme digestion. After infection with Ad-hTopoIIalpha, topo IIalpha mRNA expression in MDA-VP cells increased 7.4-fold, topo IIalpha protein production increased 5.9-fold, and sensitivity to etoposide was enhanced 4.5-fold compared with control transfected cells. Infection of normal human embryonic lung cells and human fibroblast cells with Ad-hTopoIIalpha did not enhance the expression of topo IIalpha or sensitivity to etoposide. Viral uptake was comparable in the MDA-VP and normal cell lines. These data suggest that topo IIalpha gene transfer using an adenoviral vector can selectively increase etoposide sensitivity in drug-resistant tumor cells and may enhance the therapeutic index of etoposide.
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PMID:Adenovirus-mediated human topoisomerase IIalpha gene transfer increases the sensitivity of etoposide-resistant human breast cancer cells. 1049 16

Preliminary clinical trials suggest that iodine-131 ((131)I)-labeled anti-CD20 monoclonal antibodies (MAbs) are effective single agents for the treatment of relapsed non-Hodgkin's B-cell lymphomas. However, despite high initial response rates, most patients treated in this manner will eventually relapse. We hypothesized that regimens combining (131)I-anti-CD20 antibodies with standard chemotherapeutic agents may provide synergistic anti-tumor effects, and may improve the durability of responses in patients with lymphoma. To identify promising agents for clinical testing, we assessed the in vitro cytotoxicity of combinations of (131)I-anti-B1 (anti-CD20) antibody and 8 chemotherapeutic agents using 2 human CD20-expressing lymphoma cell lines and 2 corroborative assays, the thiazolyl tetrazolium bromide (MTT) and the Trypan blue dye exclusion assays. ID(50) isobolographic and dose modification factor (DMF) analyses were used to classify interactions between the (131)I-anti-B1 antibody and the chemotherapeutic agents as supra-additive (synergistic), additive or sub-additive. Cytarabine and fludarabine were markedly supra-additive when combined with the radioimmunoconjugate, with the combination enhancing cytotoxicity 3. 5- to 5.2-fold over the level expected by simple addition of the 2 agents (DMFs 3.5-5.2). Etoposide, doxorubicin and SN-38 were moderately supra-additive (DMFs 2.0-2.8). Cisplatin and 4-hydroxycyclophosphamide exhibited merely additive cytotoxicity (DMFs 1.0-1.1). Thus, combination regimens containing (131)I-labeled anti-CD20 antibodies and nucleoside analogs or topoisomerase inhibitors appear particularly attractive for future clinical trials.
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PMID:Synergistic cytotoxicity of iodine-131-anti-CD20 monoclonal antibodies and chemotherapy for treatment of B-cell lymphomas. 1058 92


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