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)

Survival in patients with locally advanced (stage III Mo) and metastatic (Ml) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 x 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1-3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1-3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0-1) vs 14% in patients with a poor PS (ECOG 2-3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3-4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response.
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PMID:A randomized trial fo three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group. 215 54

We designed an intensive, weekly treatment regimen for patients with small-cell lung cancer (SCLC) using six of the most active chemotherapeutic agents for this disease (doxorubicin [DOX], cyclophosphamide [CTX], vincristine [VCR], etoposide [VP-16], cisplatin [CDDP], and methotrexate [MTX]). The goal of this program was to gain rapid, repetitive exposure to multiple, active drugs. Treatment was administered weekly for a total of 16 weeks. Seventy-six SCLC patients (limited disease, 34; extensive disease, 42) were treated. The overall complete plus partial response rate was 82%. Complete response rates of 47% and 38% were observed in patients with limited (LD) and extensive disease (ED), respectively. The median survivals for patients with LD and ED were 16.6 and 11.4 months, respectively. Toxicities were tolerable and were primarily hematologic. Twenty-six patients had one or more transient life-threatening toxicities, but only one patient developed a fatal toxicity. Eighty-four percent of the patients received 80% or greater of the intended protocol dosages over the entire 16-week treatment period. We conclude that this intensive, short-duration treatment regimen is at least as good as other "standard" regimens, and we are encouraged aged by the complete response rate and median survival in patients with ED SCLC.
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PMID:Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study. 217 73

The EORTC Lung Cancer Working Party investigates various chemotherapeutic regimens in patients with bronchogenic cancer. Within 12 years our Group has conducted 8 international co-operative studies in patients with non small cell lung cancer. We have demonstrated that Cis-platin was an active agent and its activity increases in association with Etoposide, mainly in limited disease. Lastly, we tested regimens including Carboplatin. This agent does not improve results in terms of objective response. We are now testing regimens including radiotherapy after chemotherapy in limited disease.
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PMID:[Chemotherapy in non-small cell bronchial carcinoma. 12 years' experience in an international cooperative group: EORTC Lung Cancer Working Party]. 217 77

A 71-year-old male underwent therapeutic pneumothorax for left pulmonary tuberculosis 42 years ago. He visited our hospital in February 1988 with a complaint of hemosputum. In October, cytology of sputum revealed malignant cells, and the patient was admitted to our hospital for further examination. Because malignant cells were found by the left bronchial lavage, pan-pleuropneumonectomy was performed on January 12, 1989 under the diagnosis of left lung cancer. The tumor was partially left unremoved. Histological diagnosis was diffuse large cell type, B cell non-Hodgkin's lymphoma. Postoperatively, 2 courses of cyclophosphamide, adriamycin, vincristine, prednisone, etoposide (CHOP and VP-16) therapy were performed. However, the patient died of respiratory insufficiency on the 125th postoperative day. Recently, cases of malignant lymphoma involving the pleura after the old tuberculous empyema and therapeutic pneumothorax have been increased. Therefore, prompt diagnosis and treatment are recommended when tumor shadow is suspected as a result of imaging examination.
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PMID:[Non-Hodgkin's lymphoma arising from the wall of old tuberculous empyema--a surgical case report]. 224 44

The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for greater than 20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4-11.8) for VP-16 and 3.4 (2.5-4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6-10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo.
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PMID:Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation. 226 55

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.
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PMID:Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer. 241 9

The relationship between morphological manifestations and cell kinetic changes of three lung cancer cell lines after exposure with chemotherapeutic agents was studied. After treatment with Cis-dichloro diammine platinum (II) (CDDP), an increase in cells of G2/M compartment at first, and then of S compartment was observed. As for the morphological manifestation, enlarged nuclear cells were more frequently observed. These cells seemed to be in S-G2/M compartment and to die finally. However a part of cells escaped from complete blockade may show multiple nuclei. Also after treatment with Etoposide (VP-16), an increase of G2/M compartment was observed, and on the morphological manifestation enlarged nuclear cells or double-or multiple-nuclear cells were observed. As these cells seemed to enter into G2/M compartment immediately. Cell destruction was thought to be started earlier compared with other two drugs. After treatment with Peplomycin (PEP), its effects on cell cycle traverse were only minimum accumulation of G2/M compartment in high PEP concentration. However concerning the morphological manifestation, many cells treated with PEP revealed enlarged, double or multiple nuclei. This suggests that morphological manifestation may reflect cytocydal effects more dominantly than cell cycle traverse. Each chemotherapeutic agent influenced the morphological manifestation and the cell kinetics of human lung cancer cells characteristically. It seemed to be important to study these relations in order to estimate the effect of chemotherapeutic agents and the therapeutic efficacy on cancer cells.
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PMID:[The relationship between morphological manifestations and cell kinetic changes of human lung cancer cells after exposure to chemotherapeutic agents]. 243 Aug 76

Although the etoposide (VP-16) and cisplatin combination has shown therapeutic activity in lung cancer, human results to date have not matched the expectation of synergism raised by animal model studies. Laboratory studies suggest that therapeutic synergism of etoposide and cisplatin may be related to factors of drug concentration, time of exposure, and sequencing. To pursue this question, we developed regimens of etoposide given by 72 h infusion in conjunction with sequential bolus or infusion cisplatin. Thirty-two patients were entered. Fourteen of 15 small-cell lung cancer patients had a response (CR, PR, regression) with a median survival of 321 days. Nine of 17 patients with non-small-cell lung cancer achieved a response, including two CRs. The median survival is 201 days. The major toxicity was myelosuppression. At the highest etoposide dosage tested, 42% of patients had leukopenia less than 2000/mm3. There were no treatment-related deaths. This new approach of combined etoposide and cisplatin therapy shows promising therapeutic activity against both small cell and non-small-cell lung cancer.
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PMID:A phase I-II study of sequential infusion VP-16 and cisplatin therapy in advanced lung cancer. 253 16

One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/- RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.
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PMID:Chemotherapy plus RA233 in the treatment of oat cell lung cancer. 254 7

The correlation between peripheral neuropathy and cisplatin (CDDP) was elucidated in 27 patients with primary and metastatic lung cancer, who were treated with Adriamycin 30 mg/m2 day 1, CDDP 80 mg/m2 day 1, and VP-16 70 mg/m2 day 1-5 every 4 weeks. The incidence of peripheral neuropathy was 33% (9 of 27 patients) and it increased to 60% in the patients who received over 320 mg/m2 of CDDP, demonstrating a positive correlation between the incidence of this toxicity and the total dose of CDDP. However, no significant relation was observed between the grade of neuropathy and CDDP. The neuropathy was manifested in the sensory system of the distal extremities and was developed into proximal portions. The peripheral neuropathy with grade 3 was irreversible, resulting in the dose-limiting factor of this regimen.
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PMID:[Peripheral neuropathy caused by cisplatin in patients with lung cancer]. 254 51


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