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)

The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Working Party conducted a randomized trial comparing cisplatin (CDDP; 120 mg/m2, day 1) and carboplatin (CBDCA; 325 mg/m2, day 1) in combination with etoposide (VP16; 100 mg/m2, days 1, 2, and 3) in advanced non-small-cell lung cancer (NSCLC). Two hundred twenty-eight patients were eligible for survival and 202 assessable for response. We obtained 27 of 100 objective responses (ORs; 27%) in the CDDP arm and 16 of 102 (16%) in the CBDCA arm (P = .07). There was no significant difference in survival. Toxicity, consisting mainly of myelosuppression and renal function impairment, was significantly increased in the patients receiving the CDDP treatment. We conclude that CDDP plus VP16 was more active but also more toxic than CBDCA plus VP16 in advanced NSCLC.
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PMID:A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. 216 53

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

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.
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PMID:Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC). 217 5

We compared cisplatin (cis-DDP) and two of its analogues, carboplatin (JM8, CBDCA) and iproplatin (JM9, CHIP) for their ability to retard the growth of multicellular tumour spheroids. The spheroids were derived from two human tumours, a neuroblastoma and a non-small-cell lung cancer. To produce a given level of regrowth delay in lung cancer spheroids, carboplatin and iproplatin were required at concentrations approximately 10 times that of cis-DDP. In the neuroblastoma spheroid experiments, iproplatin and cis-DDP produced the same level of regrowth delay when iproplatin was present at a concentration greater than 10 times that of cis-DDP. Carboplatin also required much higher concentrations than cis-DDP to produce equivalent regrowth delay in neuroblastoma. The dose-response curve produced by carboplatin on neuroblastoma spheroids displayed a pronounced shoulder in the low-dose region; this phenomenon was not seen with cis-DDP. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of lung cancer, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with cis-DDP. However, one must be cautious about generalizing on the basis of results from only two cell lines as well as applying in vitro data to clinical situations.
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PMID:The relative effectiveness of analogues of cisplatin in the experimental chemotherapy of human non-small-cell lung cancer and neuroblastoma grown as multicellular spheroids. 253 68

Carboplatin, a cisplatinum analogue, has no reported nephrotoxicity in phase I/II studies, assessed by creatinine clearance. We prospectively determined renal function in 10 untreated lung cancer patients with normal baseline renal function, treated with carboplatin 400 mg m-2 day 1 and vincristine 2 mg day 1 and 8 every 4 weeks (max. five cycles) by means of clearance studies with 125I-sodium thalamate and 131I-hippurate to determine GFR and ERPF respectively. Tubular damage was monitored by excretion of tubular enzymes and relative beta 2-microglobulin clearance. During the first course no changes in renal function were seen. After the second course a significant fall in GFR and ERPF started, ultimately leading to a median decrease in GFR of 19.0% (range 6.8-38.7%) and in ERPF of 14% (range 0-38.9%). No increases in the excretion of tubular enzymes or changes in the relative beta 2-microglobulin clearances were seen. We conclude from our data that carboplatin causes considerable loss of renal function. Monitoring renal function in patients treated with multiple courses of carboplatin is warranted.
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PMID:Acute and cumulative effects of carboplatin on renal function. 218 81

A Phase II study of carboplatin, an analog of cisplatin, was performed in patients with primary lung cancer at 17 institutions throughout Japan. Carboplatin was administered intravenously by two dosing schedules at 300 mg/m2 and 400 mg/m2. Out of 138 patients entered in the study, 101 were judged eligible for evaluation by the extramural Review Committee, and the overall response rate was 15.8% (16/101). The response rate for small-cell lung carcinoma was 25.5% (13/51) and for non-small cell lung carcinoma was 6.0% (3/50). Carboplatin was found to be effective for small-cell lung carcinoma. As for hematological toxicities, thrombocytopenia (less than 7 X 10(4)/mm3) and leukopenia (less than 3,000/mm3) were observed in 46.5% and 43.6% of cases, respectively. Nausea/vomiting was the main symptomatic side effect and was observed at an incidence of 42.6%. There was no renal, oto-or, neurotoxicities observed.
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PMID:[A phase II study of carboplatin to bronchogenic carcinoma of the lung. Carboplatin Cooperative Study Group for Lung Carcinoma]. 284 36

A phase II clinical trial of carboplatin for small cell lung cancer was conducted in 20 institutions of the National Chest Hospital lung cancer cooperative study group. Carboplatin was administered by three dosing schedule of 300 mg/m2, 400 mg/m2 and 450 mg/m2. Out of 30 patients registered in this trial, 29 patients were evaluable for response and toxicity. Seven patients achieved PR with the response rate of 24.1%. The response rates for 300 mg/m2, for 400 mg/m2 and for 450 mg/m2 were 25.0%, 8.3% and 44.4%, respectively. Thrombocytopenia (less than 7 x 10(4)/mm3) and leukopenia (less than 3,000/mm3) were observed at 25.9% and 17.2% of cases, respectively. Nausea/vomiting was also observed at an incidence of 55.2% with mild degree. No renal and ototoxic damage was observed.
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PMID:[A phase II study of carboplatin in small cell lung cancer]. 284 5

Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1a alpha,8 beta,8a alpha,8b alpha]-8-[aminocarbonyl)oxy)methyl)-4,8a- dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6- nitrosoazirino(2',3':3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1,11-diaze- tetracyclo(7.4.1.0(2,7),0(10,12]tetradeca-2-4-6-trien-6,9-++ +diyl-diacetate (FK973). In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MTT)-based assay. Average IC50 values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) = -0.788 + (0.755 x log(LD50], and relative antitumor activity, RAA (PPC/IC50), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.
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PMID:In vitro antitumor activity of mitomycin C derivative (RM-49) and new anticancer antibiotics (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay. 284 80

A 53-year-old man complained of anorexia and abdominal distention of one month's duration. The chest X-ray demonstrated a mass in the left lung with hilar and mediastinal adenopathy and a lytic lesion in the right fourth rib. A transbronchoscopic biopsy of the mass revealed oat cell carcinoma (WHO classification). The endoscopic evaluation also revealed a gastric lesion (IIc type). Biopsy of this lesion indicated signet ring cell gastric cancer. An abdominal CT scan demonstrated multiple liver metastases. Based on these findings, the patient was diagnosed as having synchronous lung and gastric primaries, with liver and bone metastasis from lung cancer. Carboplatin (CBDCA) was administered by intravenous drip infusion of 450 mg/m2. After a second treatment with CBDCA about 3 weeks later, the patient achieved a partial response at the primary site of lung cancer as well as at the liver and bone metastases. In addition, repeat endoscopy of the stomach demonstrated a complete regression. A biopsy specimen taken by gastroscopy was negative for cancer cells. Subsequent chemotherapy for small cell lung cancer was administered with cyclophosphamide, adriamycin, and vincristine, and to date there is no evidence of recurrence. Further studies on CBDCA treatment of small cell lung cancer and gastric cancer are needed to establish the efficacy of this drug against these two histologically different cancers.
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PMID:A case report of synchronous small cell lung cancer and gastric cancer successfully treated with carboplatin. 301 77

Carboplatin, a new antineoplastic agent with a spectrum of antitumor activity similar to cisplatin, has shown appreciable activity in patients with ovarian carcinoma, head and neck cancer, and small-cell lung cancer. This platinum complex is less nephrotoxic, ototoxic, and neurotoxic than cisplatin. Myelosuppression may be severe and dose-limiting. Carboplatin distributes into a volume approximating total body water, and is slowly bound to plasma proteins; its elimination is a biphasic process. Renal clearance of free platinum from carboplatin correlates highly with creatinine clearance in patients with normal or impaired renal function. The recommended iv dose of carboplatin as a single agent in previously untreated patients is 400-500 mg/m2; dosage must be reduced in patients with decreased renal function, low initial platelet count, or extensive prior chemotherapy or radiation therapy. Carboplatin will be most useful in patients with decreased renal function and those who cannot tolerate high-volume hydration regimens. Patients at higher risk for development of cisplatin-related ototoxicity or neurotoxicity (e.g., patients expected to receive cumulative cisplatin doses exceeding 600-800 mg/m2) may be ideal candidates for carboplatin as initial therapy. Large-scale comparative trials are needed before carboplatin can be recommended as a replacement for cisplatin.
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PMID:Carboplatin: a new cisplatin analog. 306 23


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