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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is the leading cause of death due to cancer in the United States, and approximately 178,100 new cases were estimated to occur last year. Small-cell lung cancer (SCLC) accounts for approximately 17% to 25% of all lung cancers. Due to its aggressive nature and rapid proliferation rate, small-cell lung cancer is usually widespread at diagnosis. Therefore, chemotherapy is the cornerstone of therapy for this disease. Cisplatin (Platinol) is an active chemotherapeutic agent used to treat small-cell lung cancer, but its toxicity, including nausea and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity, has led to the investigation of combination regimens with different toxicity profiles. Carboplatin (Paraplatin), a derivative of cisplatin, has far less nonhematologic toxicity, although myelosuppression may be slightly greater than that observed with cisplatin. The reduced toxicity and equivalent efficacy of carboplatin have resulted in the increased use of carboplatin-based regimens to treat small-cell lung cancer. Phase I and II trials of carboplatin as single-agent treatment for small-cell lung cancer resulted in overall response rates of approximately 60% for previously untreated patients and 17% for those who had received prior therapy. New combination chemotherapy regimens that include carboplatin may improve survival in patients with small-cell lung cancer and potentially cure those patients with limited disease. Further investigation of carboplatin and other new agents is warranted.
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PMID:The role of carboplatin in the treatment of small-cell lung cancer. 951 10

Chemotherapeutic intervention in advanced and metastatic non-small-cell lung cancer (NSCLC) has changed over the past 2 decades. The improvements offered by cisplatin (Platinol)-based regimens, though significant in terms of survival and quality of life, were modest at best. Carboplatin (Paraplatin), which possesses a toxicity profile favorable to that of its parent analogue cisplatin, yielded survival rates superior to that of the cisplatin-combination chemotherapy arms in a large randomized study of patients with metastatic non-small-cell lung cancer. With the introduction of taxanes in the early 1990s, paclitaxel (Taxol) demonstrated single-agent activity of 21% to 24%, with a 40% 1-year survival rate in metastatic disease. The next generation of phase I/II studies evaluated the efficacy of paclitaxel in combination with carboplatin. Results with this regimen have shown substantial promise, and 1-year survival rates as high as 54% have been reported. Full doses of both agents have been combined without any additional toxicity, and there appears to be a dose-response effect with paclitaxel. The combination of paclitaxel and carboplatin has been incorporated as the investigational arm of all the ongoing multicenter and cooperative group studies. While the results from these randomized studies are awaited, this combination has become the most widely used regimen in community practice for patients with non-small-cell lung cancer. It is also being evaluated for treatment at earlier disease stages, in the setting of minimal tumor burden, and in combined-modality regimens.
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PMID:Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. 951 17

We investigated the efficacy of combination of ondansetron hydrochloride injection and tablet against nausea and vomiting in 22 lung cancer patients (total number of chemotherapy courses: 23) receiving chemotherapy of single-dose carboplatin (CBDCA) at a dose of 302.2 +/- 31.9 mg/m2. For suppressing emesis, the patients were given 4 mg of ondansetron injection on the day of CBDCA injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 5. The following results were obtained 5 days after the administration of carboplatin. 1) Control of nausea graded 'Good' or better counted for 95% or higher of all cases for each day of the chemotherapy. A complete nausea suppression rate was seen in 91.3%, 81.0%, 71.4%, 63.6% and 71.4% from Day 1 to Day 5, respectively. 2) Control of vomiting graded 'Major' control or better was achieved in 95% or more of all cases, for each day. The complete vomiting suppression rate observed from Day 1 to Day 5 was 91.3%, 78.3%, 65.2%, 69.6% and 91.3%, respectively. 3) Inhibitory effect on nausea and vomiting for each day of Days 1 to 5 graded as 'Effective' or better was shown in 90% or higher of all cases; based on overall judgement for Days 1 to 5, all cases were graded as 'Effective' or better. 4) The proportion of cases which was evaluated as 'Can eat most of the meal' was 88.0%, 73.9%, 50.7%, 50.7% and 65.2% from Days 1 to 5, respectively, against 95.7% prior to the start of chemotherapy. 5) No adverse drug reaction or abnormal clinical laboratory values were seen along with ondansetron. 6) In conclusion, combined treatment with ondansetron injection and tablet was considered clinically useful in control of nausea and vomiting during administration of carboplatin, and may also be useful for out-patient chemotherapy.
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PMID:[Effect of ondansetron hydrochloride injection and tablet against nausea and vomiting in lung cancer patients receiving carboplatin]. 998 8

Sixty patients with poor prognostic features, either with extensive disease (ED) or limited disease (LD) small cell lung cancer (SCLC), were treated on an out-patient basis with Carboplatin 80 mg/m2 weekly for 3 weeks and oral Etoposide, at a dose of 100 mg, every other day for 21 days. The treatment was repeated every 5 weeks. Responding patients with LD were also treated with thoracic irradiation and those who achieved complete response (CR) received prophylactic cranial radio-therapy. The overall response rate (RR) was 32.1% with 8.9% CR. The responses were better for LD (RR 58.3%, CR 25%, partial response, PR 33.3%), than those for ED (RR 25%, CR 4.5%, PR 20.5%). The median time to progression (TTP) was 4.8 months and the median survival 5.5 months. These poor results could be attributed to the bad performance status and the presence of visceral and brain metastases in this group of patients. The results could also be due to the lower maximum concentration (Cmax) and higher T1/2 of Etoposide, as measured in the blood and urine probably due to the modified regimen used in our study and to the organ insufficiency in this selected group of patients. Although, toxicity was generally mild and manageable, two toxic deaths occurred. In conclusion, this regimen appears to have a lower efficacy in terms of response and survival than that obtained in other studies using Cisplatin or Carboplatin plus Etoposide in a similar way. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and ECOG performance status > or = 2.
Lung Cancer 1999 Feb
PMID:Combination chemotherapy with low doses of weekly Carboplatin and oral Etoposide in poor risk small cell lung cancer. 1021 20

Small cell lung cancer (SCLC) will account for approximately 20%-25% of the 171,500 estimated new lung cancer cases in 1998. Combination cytotoxic therapies have yielded the best response rates in SCLC patients. Cisplatin in combination with etoposide is used routinely in the treatment of SCLC. Because of cisplatin's nonhematologic toxicities, carboplatin was developed and has far fewer nonhematologic toxicities. Carboplatin in combination with etoposide has been shown to be as effective as, but less toxic than, cisplatin/etoposide. Moreover, carboplatin/etoposide is a viable combination in the treatment of the elderly with SCLC, who can readily tolerate this combination. Concurrent radiation therapy with carboplatin and etoposide in patients with limited SCLC disease can be given safely and effectively. Carboplatin has been combined with several different chemotherapeutic agents, including ifosfamide, and, more recently, paclitaxel in hopes of improving the response rates and overall survival. In order to try to dose intensify carboplatin-based regimens, peripheral blood stem cells have been used to decrease the hematologic toxicities. Further studies are warranted to investigate these therapies as well as newer carboplatin combinations.
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PMID:Carboplatin in the Treatment of Small Cell Lung Cancer. 1038 98

Optimal treatment in elderly (> 70 years) with stage IV non-small cell lung cancer (NSCLC) is not known. In order to define it, concurrent short-term chemotherapy (CHT) and palliative radiotherapy (RT) was evaluated in this patient population. Between January 1988 and June 1993, a total of 50 patients entered into a study that used two cycles of carboplatin (CBDCA), 300 mg/m2, days 1 and 29 and oral etoposide, 50 mg/m2, days 1-21 and 29-42. RT was administered with dose of 14 Gy in two fractions given with 1 week split, days 1 and 8. Of 47 patients evaluable for the response, there were three (6%) complete response (CR), and ten (21%) partial response (PR), making the overall response rate of 13 (28%). Response duration ranged 2-8 months (median, 5 months; mean, 5 months). Median survival time (MST) for all 50 patients was 7 months and 1-3 year survival rates were 31, 4.1, and 2%, respectively. There were only nine (19%) patients experiencing hematological grade 3 toxicity, all other CHT-induced toxicity being grade 1 or 2. Of RT-induced high-grade toxicity, grade 3 esophageal was observed in nine (19%) patients while only four (9%) patients experienced grade 3 bronchopulmonary toxicity. No grade 4 or 5 toxicity occurred during this study. Short-course CHT and palliative RT in elderly patients with stage IV NSCLC was well tolerated with mild to moderate toxicity. Together with results obtained this way, they warrant further studies evaluating the effectiveness of this approach and possible CHT- and/or RT-dose escalation in elderly patients with stage IV NSCLC.
Lung Cancer 1999 Apr
PMID:Short-term chemotherapy and palliative radiotherapy for elderly patients with stage IV non-small cell lung cancer: a phase II study. 1040 88

Irinotecan (CPT-11) and carboplatin have broad anti-tumor activities. We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer. The aim of the study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this regimen. In addition, we prospectively evaluated the Chatelut formula for predicting carboplatin clearance. Patients with advanced cancer were treated with CPT-11 (days 1, 8, and 15) and carboplatin (day 1) of a fixed-target area under the concentration-time curve (AUC) of 5 mg x min/ml. Carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The CPT-11 dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2. A total of 27 patients, 26 lung cancer patients and 1 colon cancer patient, were enrolled in this study. Dose-limiting leukoneutropenia, thrombocytopenia, and diarrhea, including one treatment-related death, were observed at 60 mg/m2 CPT-11, indicating that this level was the MTD. In 11 patients, the actual AUCs of carboplatin almost achieved the target AUC of 5. Fifteen (60%) of 25 evaluable patients showed an objective response, with an 85% response rate [11 of 13 patients (complete response, 31%; partial response, 54%)] in small cell lung cancers and a 36% response rate (4 of 11 patients) in non-small cell lung cancers. Neutropenia, thrombocytopenia, and diarrhea were the dose-limiting toxicities in this regimen. CPT-11 (50 mg/m2) under the carboplatin target AUC of 5 using the Chatelut formula was the recommended dose for further Phase II study, and this regimen seems to be active for small cell lung cancer.
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PMID:Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers. 1063 26

The antitumor efficacy of the combination of nedaplatin (NDP) with gemcitabine (GEM) was evaluated. We also compared the antitumor activity of NDP plus GEM with that of cisplatin (CDDP) plus GEM or carboplatin (CBDCA) plus GEM. Ma44, which is a human lung cancer sensitive to GEM, and NCI-H460, which is a human lung cancer refractory to GEM, were used in this study. GEM was injected i.v. once followed by i.v. injection of NDP at an interval of approximately 30 min into tumor-bearing athymic mice. GEM was administered again 3 or 4 days thereafter. Combined dosing of NDP with GEM resulted in synergistically enhanced inhibition of tumor growth in the Ma44 tumor model. NDP plus GEM was also effective against Ma44 cells when given late in the therapy, a model for advanced disease. Potent augmentation of growth inhibition by NDP with GEM was also found with the NCI-H460 tumor model. The combination effect of NDP plus GEM appeared to be superior to that of CDDP plus GEM or CBDCA plus GEM in both tumor models. Toxicity in terms of blood cell numbers was not enhanced by the combination of NDP with GEM. These results suggest the effectiveness of combination of NDP with GEM for clinical therapy.
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PMID:Preclinical in vivo antitumor efficacy of nedaplatin with gemcitabine against human lung cancer. 1117 44

Combinations of gemcitabine (Gemzar) with cisplatin (Platinol) are among the most active new chemotherapy regimens developed for advanced non-small-cell lung cancer. Carboplatin (Paraplatin) is a platinum analog devoid of many of the nonhematologic toxicities associated with cisplatin. Although few direct comparisons have been made, when administered by area under the concentration-time curve (AUC) dosing, carboplatin is probably equivalent to cisplatin in advanced non-small-cell lung cancer and provides an improved therapeutic index. Based on its favorable toxicity profile, carboplatin has supplanted cisplatin for use in combination with paclitaxel in several different tumor types. Initial trials combining gemcitabine and carboplatin using standard days 1, 8, and 15 dosing of gemcitabine suggested that thrombocytopenia was problematic. More recently, 21-day schedules in which gemcitabine is administered only on days 1 and 8 have demonstrated both efficacy and improved toxicity profiles. Here we review recent studies investigating gemcitabine plus carboplatin and preliminary data regarding combinations of gemcitabine with the new platinum analog oxaliplatin.
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PMID:Gemcitabine in combination with new platinum compounds: an update. 1130 43

To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure. MRP3 and MRP4 gene expression levels were monitored in the PMN of 10 previously untreated lung cancer patients within 24 hr after carboplatin (CBDCA) administration. Expression levels for both genes were also examined in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients with lung cancer. MRP3 and MRP4 gene expression levels were assessed by quantitative reverse transcription-polymerase chain reaction. MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same. Furthermore, MRP3 expression levels in normal lung and tumor tissues from autopsy samples that had been exposed to platinum drugs while the patients were alive were significantly higher than those in unexposed tissues, but again MRP4 expression levels remained the same. These results suggest that platinum drugs and/or the physiological stress response to xenobiotics induce expression of the MRP3 gene.
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PMID:Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer. 1147 64


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