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)

Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
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PMID:Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting. 166 19

Epirubicin (4'-epidoxorubicin), an analogue of doxorubicin (Adriamycin), has established activity in the treatment of small-cell lung cancer (SCLC) when used at doses of 75 to 120 mg/m2 in previously untreated patients. We completed a phase II study of epirubicin (85 mg/m2 given intravenously at 3-week intervals) in 20 patients with recurrent SCLC, all of whom had received prior combination chemotherapy. Of 19 patients who were assessable for response, 2 achieved a complete response and 2 a partial response, for an overall response rate of 4/19 (21%); 95% confidence interval, 8%-43%). Myelosuppression and alopecia were the most frequent toxicities; epirubicin was otherwise well tolerated, with other toxicities such as nausea and vomiting being infrequent or mild. Epirubicin at a dose of 85 mg/m2 exhibits modest single-agent activity in previously treated SCLC and is generally well tolerated. Given as a single agent or in combination with other well-tolerated drugs, epirubicin would be suitable in cases in which palliation of symptoms without undue toxicity is required in the management of previously treated SCLC.
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PMID:Epirubicin: a phase II study in recurrent small-cell lung cancer. 171 30

The effects on gastric and duodenal mucosa induced by cisplatin plus etoposide (PE) chemotherapy were investigated in 32 patients with lung cancer. They were submitted to gastroduodenoscopy before receiving cisplatin 100 mg/m2 (day 1) plus etoposide at a mean dose of 107 mg/m2 (days 1, 3 and 5). Endoscopic examination was repeated on day 8. Before chemotherapy, 22 patients showed normal endoscopic appearance and 10 minimal lesions (3 or fewer erosions). After chemotherapy, 16 remained normal, 1 had minimal lesions and 15 developed major lesions: 11 gastric or duodenal multiple erosions, 1 diffuse erosive gastritis, 2 gastric and 1 duodenal ulcer (p less than 0.001). No difference was observed in the number of vomiting episodes nor in severity of upper gastrointestinal symptoms between the patients who remained normal and those who developed mucosal injury. We conclude that PE chemotherapy can have a properly called gastroduodenal toxicity, leaving nausea and vomiting out which are rather due to central than peripheral mechanisms. Some trials are necessary to investigate which kind of drugs (H2-receptor blockers, sucralfate, prostaglandin E analogues) may be useful in preventing acute gastroduodenal mucosal injury induced by PE chemotherapy.
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PMID:Acute gastroduodenal mucosal injury after cisplatin plus etoposide chemotherapy. Clinical and endoscopic study. 174 80

A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC). Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features. The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks. Dose modifications were made according to defined hematologic criteria. Responding patients with limited disease subsequently received mediastinal radiotherapy. Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%. Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%. Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks). Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens. In all, one quarter of treatment courses were delayed, most frequently because of leukopenia. Dose reductions were required in 63% of cases. The average delivered dose intensity was calculated and shown to be 73% of projected. Nonhematologic toxicity was mild with nausea and vomiting being the most common. This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.
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PMID:Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer. 184 6

Usefulness of alprazolam for control of chemotherapy-induced emesis including 5-day continuous intravenous infusion of cisplatin for advanced lung cancer was evaluated by a randomized crossover design. Of 22 cases evaluated, 8 in the alprazolam group and 1 in the untreated group were free from nausea and vomiting (p less than 0.01). The mean frequency of vomiting in the alprazolam group was 1.18 times, which is significantly smaller than 2.25 times in the untreated group (p less than 0.05). The mean duration of vomiting and nausea was significantly shorter in the alprazolam group (p less than 0.01, p less than 0.05). It is thus concluded that concomitant therapy with the minor tranquilizer alprazolam is useful in treating cisplatin-induced acute or delayed emesis in which psychological and psychiatric factors are involved.
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PMID:[Usefulness of alprazolam in controlling cisplatin-induced emesis]. 184 92

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.
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PMID:Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. 215 94

Chemotherapy with mitomycin C, ifosfamide and cisplatin (MIC) is reported to produce responses of 56% and 69% in inoperable non-small-cell lung cancer (NSCLC). We evaluated the regimen in 45 similar patients who received up to six courses of 6 mg/m2 mitomycin C, 3 g/m2 ifosfamide, and 50 mg/m2 cisplatin every 3 weeks. In all, 18 patients had limited disease (LD) and 27 had extensive disease (ED). A total of 18 patients responded (40%), 9/18 with LD and 9/27 with ED; there were 4 complete responders. The median duration of response was 25 weeks, and median survival was 32 weeks (range, 2-96 weeks). Toxicity was moderate. Nausea and vomiting were controlled with i.v. dexamethasone and high-dose metoclopramide. Other toxicities included myelosuppression and alopecia. This study confirms that MIC is one of the most active regimens for treatment of NSCLC, with acceptable toxicity.
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PMID:Mitomycin, ifosfamide and cisplatin in non-small-cell lung cancer. 215 66

The Clinical Trials Group of the National Cancer Institute of Canada (NCIC) studied single-agent epirubicin in 40 previously untreated patients with extensive small-cell lung cancer (SCLC). The starting dose of epirubicin was 100 (eight patients) or 120 (32 patients) mg/m2 administered intravenously every 3 weeks. Twenty patients (50%) achieved an objective response (95% confidence limits, 33% to 66%) and three of the 20 had complete responses (CRs). The median survival of all 40 patients was 8.3 months (35.4 weeks). Myelosuppression, mild or moderate nausea and vomiting, and hair loss were commonly seen. There was one chemotherapy-related death. This drug is active and well tolerated in SCLC and the use of it as first-line therapy did not appear to compromise survival in this group of patients.
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PMID:Epirubicin in extensive small-cell lung cancer: a phase II study in previously untreated patients: a National Cancer Institute of Canada Clinical Trials Group Study. 215 6

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.
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PMID:Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer. 215 6

A combination phase II study was performed on 31 patients with previously untreated small-cell lung cancer (19 LD & 12 ED). Patients were treated intravenously with Adriamycin (30 mg/m2 day 1), CDDP (80 mg/m2 day 1) and Etoposide (70 mg/m2 x 3 day 1, 3, 5). This combination chemotherapy was administered over a four- or five-week period. Among 26 evaluable patients there were 4 CR and 17 PR, giving a response rate of 80.8% (68.4% in LD). The median duration of response was 19 (3-123) weeks. Despite the relatively low response rate and CR rate, the median survival times of LD and ED patients were 17.0 (3.1-43.1) and 9.4 (4.4-17.7) months, respectively. The major toxic effect of this regimen was bone marrow suppression. Two patients were excluded from this study in the first course because of severe hematologic toxicity. The renal toxicity of this regimen was minimal and no patients developed any clinical problem. Nausea and vomiting during the treatment were well controlled by high-dose metoclopramide and methylprednisolone. In conclusion, this combination of chemotherapy is effective for patients with small cell lung cancer. However, the advantage of adding Adriamycin to CDDP and Etoposide is still controversial.
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PMID:[A combination phase II study of adriamycin, CDDP and etoposide in small cell lung cancer]. 215 85


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