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)

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.
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PMID:Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer. 216 38

A total of 51 previously untreated patients with non-small-cell lung cancer (NSCLC) were treated with 130 mg/m2 carboplatin given every 4 weeks as an i.v. infusion on days 1, 3, and 5. Ten patients achieved a partial response and five, a minor response. The overall response rate was 20% (95% confidence limits, 8%-32%). The median duration of response was 3 months and the median overall survival was 4.5 months. Leucopenia, thrombocytopenia and anemia of WHO grade 3 occurred in 4%-6% of patients and grade 3 nausea and vomiting was observed in 8% of our subjects. Grade 4 thrombocytopenia occurred in 3 (6%) patients. Apart from nausea and vomiting, nonhematologic toxicities above grade 2 were not observed. Further trials using carboplatin in NSCLC as a single agent or in combination with other chemotherapeutic agents or radiation are warranted.
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PMID:Phase II study of carboplatin in untreated, inoperable non-small-cell lung cancer. 217 44

A total of 68 patients with non-small-cell lung cancer who either had not previously been treated (38) or had undergone prior therapy (30) were treated in a phase II study of (glycolate-O,O') diammineplatinum(II) (NSC 375 101D; 254-S), a new platinum complex. The drug was given as a single intravenous infusion at a dose of 100 mg/m2 every 4 weeks. All 68 patients could be evaluated for response and 62, for toxicity. Objective responses were seen in 10 of 68 cases (14.7%; 95% confidence interval, 7.3%-25.4%), and the median duration of response was 15 weeks (range, 8-23 weeks). The response rates were similar for previously untreated and treated patients (13% and 17%, respectively), including three previously treated with cisplatin. Myelosuppression was the dose-limiting toxicity. Thrombocytopenia (less than 100,000 platelets/mm3) and leukocytopenia (less than 3,000 WBC/mm3) were observed in 22 (35%) and 18 (29%) patients, respectively. Mild to moderate nausea and vomiting occurred in 45 cases (73%). No significant renal or neurotoxicity was observed. We conclude that as a single agent, 254-S is well tolerated but appears to have marginal activity against non-small-cell lung cancer.
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PMID:Phase II study of (glycolate-O,O') diammineplatinum(II), a novel platinum complex, in the treatment of non-small-cell lung cancer. 217 94

Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.
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PMID:Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study. 217 40

A total of 42 evaluable patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of cisplatin (80 mg/m2, day 1), vinblastine (5 mg/m2, days 1 and 15), and ifosfamide (1.2 g/m2, days 1-3). In all, 1 complete response and 15 partial responses were obtained, for an overall response rate of 38% (95% confidence limits, 23.6%-54.4%). The median duration of response was 15 weeks, and the median overall survival was 56 weeks. Toxicity mainly consisted of moderate to severe alopecia in 28 patients (67%), moderate to severe nausea and vomiting in 27 subjects (64%), and leukopenia comprising less than 1,000 leukocytes/mm3 in 6 cases (14%). In all, 16 patients (38%) had microscopic hematuria (WHO grade 1), but no hemorrhagic cystitis was documented. Although this three-drug combination appears to have moderate antitumor activity against non-small-cell lung cancer, the addition of ifosfamide to the combination of cisplatin and vinblastine did not seem to improve the response rate.
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PMID:Ifosfamide, cisplatin, vinblastine combination chemotherapy in the treatment of advanced non-small-cell lung cancer. 217 35

We have carried out the Phase II study by oral administration of UFT enteric-coated granules (UE) against various malignant tumors. Out of 45 patients entered in the study, 40 patients were evaluable: 36 patients among them had measurable lesions. PR (partial response) were obtained in two (11.1%) out of 18 patients with gastric cancer and one (50.0 %) out of 2 patients with lung cancer. Total response rate was 8.3%. Side effects by UE were slight; that is, anorexia (13.3%), nausea and vomiting (8.9%), generalized malaise (8.9%) and so forth. UE, as a long-term therapy, can be considered a useful drug against cancers with less side effects.
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PMID:[Clinical results of UFT enteric-coated granule therapy under cooperative study (phase II study). Tokyo Cancer Chemotherapy Cooperative Study Group]. 222 28

As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial.
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PMID:Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. 224 91

Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.
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PMID:Toxicity of FED chemotherapy in non-small-cell lung cancer. 244 89

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.
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PMID:[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group]. 245 15

A total of 45 patients with locally advanced and/or metastatic non-small-cell lung cancer (NSCLC) were treated in a phase II trial with high-dose i.v. infusions of 24 g hydroxyurea over 24 h, with 50 mg/m2 i.v. cisplatin 8 h after the start of hydroxyurea infusion. Hydroxyurea, a cell-cycle-specific inhibitor of ribonucleotide reductase, inhibits DNA repair by depleting nucleotide pools. We gave hydroxyurea to achieve steady-state levels of greater than or equal to 1 mM and to potentiate therapy by inhibiting repair of DNA damage produced by cisplatin. Among 21 patients with squamous cell lung cancer, there were 1 complete response (CR), 2 partial responses (PR) and 3 minor responses (MR). Of 13 patients with adenocarcinoma of the lung, 2 had MRs; of 11 patients with large-cell anaplastic lung cancer, none responded. The dominant toxicity was nausea and vomiting, which was manageable and mainly related to cisplatin. The response rate in squamous cell lung cancer was similar to responses obtained with cisplatin alone. The relative ineffectiveness of high-dose 24-h infusions of hydroxyurea in inhibiting repair of DNA damage produced by cisplatin may be due to the low growth fraction of human NSCLC. The high-dose hydroxyurea approach may be more applicable in tumours with a high growth fraction.
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PMID:Cisplatin with high-dose infusions of hydroxyurea to inhibit DNA repair. A phase II study in non-small-cell lung cancer. 253 51


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