Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cis-Dichlorodiammine platinum (II) (cis-DDP) was demonstrated to be a potentiator of radiation therapy (RT) in experimental tumor models and in cultured cells. To assess the effectiveness of a combined modality treatment including RT and a weekly low-dose administration of cis-DDP, from January 1986 to June 1987, 95 patients with unresectable locally advanced non-small cell carcinoma of the lung (stage IIIa, b) were randomized for study. Fifty patients received RT alone at doses of 50 Gy; 45 patients received the same RT plus cis-DDP 15 mg/m2 IV weekly. An overall response rate of 50% and 64% was observed in the RT and RT + cis-DDP group, respectively. No statistically significant differences were detected with regard to median survival time (11 months for RT v 16 months for RT + cis-DDP) and progression-free interval (7 months in the RT arm v 9 months in the RT + cis-DDP arm), but the patterns of the first failure appeared to be affected by treatment. In fact, a lower number of intrathoracic relapses was observed in the RT + cis-DDP arm (12 in the RT + cis-DDP v 23 in the RT arm). Toxicity was mild and the feasibility of this schedule must be remarked. A better local control of disease can be obtained using cis-DDP as a radiation potentiator, but the true influence of this combined modality treatment on the length of survival, and the optimal cis-DDP timing and dosage are still to be evaluated in further clinical trials.
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PMID:A randomized clinical trial comparing radiation therapy v radiation therapy plus cis-dichlorodiammine platinum (II) in the treatment of locally advanced non-small cell lung cancer. 285 Nov 72

In a prospective randomized study 150 patients with small cell lung carcinoma (80 cases with extended, 70 cases with limited disease) received either cisplatin + etoposide (DDP/VP) or cyclophosphamide + etoposide (cyclo/VP) as induction chemotherapy. Patients were crossed over when less than complete remission was achieved. Treatment failures received a salvage regimen with adriamycin + vindesine (ADM/VDS). Remission rates (complete + partial remissions) achieved with DDP/VP were 87.4% (40.6% + 46.8%) in limited disease and 72.2% (10.1% + 62.1%) in extended disease; response rates seen following cyclo/VP were 78.8% (31.5% + 47.3%) in limited and 51.0% (6.9% + 44.1%) in extended disease. Median survival time for patients in complete remission was 12.0 months following DDP/VP and 14 months following cyclo/VP; for patients in partial remission 10.0 and 9.0 months, respectively. The analysis of the treatment results shows an equal effectivity of both induction regimes which, however, seem to be largely cross resistant. DDP/VP probably causes more stable longtime remissions. The salvage regimen ADM/VDS was ineffective. The results achieved with this rather complex therapeutic strategy are not superior to those seen with simpler regimes.
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PMID:[Phase III therapy study in patients with small cell bronchial cancer]. 285 62

In all, 171 patients with histologically verified non-small cell lung carcinoma were treated with ifosfamide 2.0 g/m2 on days 1-5 in combination with (91 patients) etoposide 120 mg/m2 on day 1. Therapeutic regimens were repeated after 4 weeks. Supportive treatment with mesna (20% of the ifosfamide doses at 0, 4, and 8 h) was performed. Cisplatin treatment was supported by mannitol-induced diuretic hydration. The overall response rate of ifosfamide/etoposide was calculated to be 27%, with 1 complete and 24 partial remissions. The median survival time for all patients was 8.5 months, for responders 14 months (P less than 0.05), for patients with no change 9.5 months, and for patients with tumor progression 4 months. With ifosfamide/cisplatin, there were 4 complete and 21 partial remissions (response rate 35%). The median survival time for all patients was 8.3 months, for responders 11.5 months, and for patients with tumor progression 4 months. Age, sex, and histological tumor type had no significant effect on survival. Patients with better performance stage and limited disease lived significantly longer. The main side-effects of the cisplatin combination were vomiting, bone marrow depression, and neuropathy. The etoposide combination was tolerated better. Urotoxicity was not significant, as a consequence of treatment with mesna. The results show that the combination ifosfamide/etoposide or ifosfamide/cisplatin are effective in the treatment of non-small cell lung cancer, being comparable to other combinations of etoposide/cisplatin and vindesine/cisplatin. Because of the better tolerability, the combination ifosfamide/etoposide is superior to cisplatin combinations.
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PMID:Experience with ifosfamide combinations (etoposide or DDP) in non-small cell lung cancer. 302 62

Doxorubicin (DXR) has a positive inoculum effect and penetrates poorly into the core of multicellular tumour spheroids (MTS). Cis-platin (DDP) displays neither of these characteristics. We evaluated whether combining these 2 agents would influence the cell kill effect at a tumour mass level. MTS were produced from a PC-10 squamous lung carcinoma cell line. MTS were exposed to either drug first for 1 h with different intervals between exposure. Cells were then trypsinized to a single cell suspension and subjected to clonogenic assay. Combination effects were analyzed by median effect plot analysis. The more MTS ml-1 medium, the lower the cell kill effect of DXR. Simultaneous exposure to the 2 drugs was synergistic. DXR exposure first followed by DDP was less efficacious than, or the same as, the simultaneous exposure. In contrast, DDP followed by DXR was more efficacious with the best cell kill at a 1 h interval between each drug. This phenomenon was observed even at non-toxic doses of DDP. The fluorescent microscopic study of DXR indicated that prior exposure of MTS to DDP resulted in increased DXR penetration into the MTS core leading to heightened synergism with this sequence. These data suggest that the proper combination of DXR plus DDP should be in sequence with DDP first. Clinical, toxicological and pharmacological trials of DDP administration first, followed by DXR, are warranted.
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PMID:Interactions of doxorubicin and cis-platin in squamous carcinoma cells in culture. 317 85

We report a case of a 60-year-old woman affected by squamous lung carcinoma, who developed paroxysmal supraventricular tachycardia during cisplatin and etoposide combination chemotherapy. Cisplatin toxicity on cardiac electrical activity is discussed. This observation might suggest caution when cisplatin is used in patients with cardiac disease or pretreated with other potential cardiotoxic antineoplastic agents.
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PMID:Paroxysmal supraventricular tachycardia during treatment with cisplatin and etoposide combination. 372 84

The effects of chemotherapy by single administration of Cisplatin were studied in 26 patients with non-small cell carcinoma of the lung. There were 22 males and 4 females with a median age of 63 years. 21 cases were epidermoid carcinoma, 4 cases were adenocarcinoma and 1 case was atypical carcinoid. Cisplatin 20 mg/m2 with hydration and diuresis was given daily for 5 consecutive days. The course was repeated every 3 weeks. Partial response was observed in 4 patients (3 epidermoid carcinoma and one atypical carcinoid). The response rate was 19%. Side effects induced by Cisplatin were gastrointestinal toxicity including vomiting, nausea and appetite less, bone marrow toxicity and renal damage. These were not so severe, and reversible. Gastrointestinal toxicities were controlled successfully by corticosteroids. In 12 patients gastrointestinal toxicities were not observed. We conclude that Cisplatin is effective for non-small cell carcinoma, especially for epidermoid carcinoma. Hematologic toxicities of Cisplatin were not so severe. Therefore, combination chemotherapy including Cisplatin would improve the quality of life of patients suffering from non-small cell carcinoma of the lung.
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PMID:[The evaluation of single administration of cisplatin in non-small cell carcinoma of the lung]. 404 Mar 52

We have established a model for malignancy-associated humoral hypercalcemia (MAHH) in athymic mice, utilizing a human squamous cell lung carcinoma. In the present studies, we evaluated cis-platinum (DDP), a cytotoxic agent known to produce hypomagnesemia, and occasionally hypocalcemia, in the treatment of MAHH. Upon development of significant hypercalcemia, defined as serum calcium (Ca) greater than or equal to 11.5 mg/dl, tumor-bearing mice received either normal saline (NS) alone (1.5 ml/day, i.p.), or NS + DDP. The DDP was given as a single dose of 6 micrograms/g body weight i.p. Serum Ca was determined on day 6 in surviving mice (6 of 10 survived in the NS-alone group; 7 of 10 survived in the NS + DDP group). Serum Ca (mean +/- SE) decreased from 14.3 +/- 0.46 to a nadir of 12.7 +/- 0.33 mg/dl in the NS-alone group, and from 13.5 +/- 0.46 to a nadir of 10.4 +/- 0.48 mg/dl in the NS + DDP group. Nadir serum Ca levels were significantly lower in the NS + DDP group (P = 0.003). Three of 7 surviving NS + DDP mice achieved normocalcemia, whereas none of the NS-alone animals became normocalcemic. Tumor volumes increased in all animals. There was no change in the serum Ca in 5 tumor-free mice treated with NS + DDP. There were no significant differences in serum magnesium levels among groups of control mice, tumor-free mice treated with NS + DDP, tumor-bearing mice treated with NS + DDP, and tumor-bearing mice treated with NS-alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cis-platinum treatment for malignancy-associated humoral hypercalcemia in an athymic mouse model. 644 29

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.
Lung Cancer 1995 Apr
PMID:A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer. 755 36

In scheduling chemotherapy and radiotherapy for locally advanced non-small cell lung cancer (NSCLC), chemotherapy can be given pre-radiotherapy or concurrently as a single agent or in combination. Optimal scheduling has yet to be established. Optimal pre-radiotherapy for NSCLC requires further development but cisplatin with vinblastine, vindesine, etoposide or navelbine appear the best currently available. A number of new drugs show potential for enhancing radiation effects. Concurrent chemotherapy and radiotherapy has been tested in a number of experimental tumours in cell culture. In these systems cisplatin, carboplatin, 5-fluorouracil, mitomycin-C and other agents appear to improve cell kill compared to chemotherapy alone. Mouse xenograft models allow the study of various concurrent drug and radiation schedules including the effect of radiation with cisplatin, carboplatin, paclitaxel and gemcitabine. In these systems, cisplatin in divided doses shows optimal enhancement with fractionated radiotherapy. There are a number of drug candidates for concurrent chemotherapy and radiotherapy programs. Clinical studies in head and neck cancer, esophageal cancer, small cell lung cancer and NSCLC show promising results with concurrent chemotherapy and radiotherapy. Cisplatin given daily with radiotherapy improved survival in NSCLC compared to cisplatin given weekly with radiotherapy or to radiotherapy alone. To study the toxicity of radiation and concurrent carboplatin, we have studied 170 patients with unresectable locally advanced NSCLC in a 4-arm randomized trial. An analysis of the first 100 patients entered revealed significantly more neutropenia (P < 0.0001) and thrombocytopenia (P < 0.004) with the combined modality arms. Esophagitis was worse on all three experimental arms but was significantly more prolonged with accelerated radiotherapy arms.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung Cancer 1995 Jun
PMID:Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. 755 50

The Br/Rb ratio in kidneys of normal and tumor-bearing mice was studied and a significant difference was found between the two groups. The mice were treated with cis-DDP with and without selenite, with selenite alone, and compared with controls. The animals were sacrificed 7d, 14d, and 21-28d after treatment. The kidneys were removed and subjected to Br and Rb determination by a novel X-ray fluorescence (XRF) method. The results are presented in terms of estimated net count rates under the BrK alpha and RbK alpha peaks. No significant differences were found in Br and Rb levels or in the Br/Rb ratio in kidneys of treated and untreated mice belonging to the same group-normals or lung carcinoma inoculated. However, there was a significant difference in the Br/Rb ratio between the two tested groups (normals and inoculated). Preliminary results on the Br/Rb ratio obtained from normal and malignant tissues of colorectal cancer (CRC) patients and from mice inoculated with melanoma, show the same trend as those from the group of mice with lung carcinoma. In all three groups tested the Br/Rb ratio was 2-4 times higher in normal than in malignant tissue.
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PMID:Br/Rb ratio obtained by XRF analysis of kidneys of normal and tumor-bearing mice treated with cis-DDP. 759 9


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