Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high activity of carboplatin as a single agent in small cell lung cancer was first identified in 30 previously untreated patients who had a 60% response, which included a 10% complete remission (CR). In this and subsequent studies, carboplatin showed high activity without the nephrotoxicity and neurotoxicity associated with cisplatin. Gastrointestinal side effects and alopecia were also generally mild; the major toxicity was myelosuppression. Two important studies of carboplatin 300 mg/m2 and etoposide (300 to 400 mg/m2) in divided doses have reported objective responses of 85% (21% CR) and 65% (21% CR) in previously untreated patients. However, the median survival in the first study was only 9.5 months in both limited- and extensive-stage patients. In this study, 19% of patients had substantial dose reductions because of myelosuppression. The second study reported a better median survival of 15.3 months for limited-stage patients and 8.3 months for extensive-stage patients. These patients received a maximum of six courses of chemotherapy as opposed to four in the first study, and cranial irradiation in addition to mediastinal irradiation. There also appeared to be fewer dose reductions, ie, 11% for carboplatin. Another study using the combination of carboplatin and etoposide in extensive-stage patients only reported a 56% response rate, including 16% CR and a median survival of 8.1 months. The major toxicity in these three studies was myelosuppression, particularly leukopenia, but only three neutropenia-associated deaths occurred in a total of 180 patients. A recent study has reported the use of similar doses of carboplatin and etoposide in combination with ifosfamide 5 g/m2 (with mesna) and midcourse vincristine. Thoracic radiotherapy was given after six courses of chemotherapy in responding patients, but no cranial irradiation was used. In 42 patients, 30 of whom had limited-stage disease, the response rate was 78%, including a 57% CR rate. The median survival was 14 months, and the 2-year actual survival rate is 33%. These and other studies of carboplatin combinations (which are only preliminary) have described high response rates and possibly improved survival compared with less intensive therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carboplatin in small cell lung cancer. 215 59

Forty-two patients with small cell lung cancer were treated with a combination of carboplatin, ifosfamide and etoposide. Vincristine was given on day 14 of each course, the courses being repeated every 28 days for a maximum of six. Thoracic radiotherapy was given 4 weeks after the last course of chemotherapy but no prophylactic cranial radiotherapy was administered. Thirty patients had clinically limited state disease, the remaining patients having contralateral neck lymphadenopathy and/or pleural effusions. Elevated enzyme levels (alkaline phosphatase, LDH, ALT, GGT) were noted in 69% of patients. Twenty-four patients (57%) achieved a complete response (CR) when assessed one month after the end of treatment. A further 21% of patients had a partial response (PR). Median duration of CR was 14 months and of PR 8 months. Cerebral metastases were the sole site of relapse in 13% of the CR patients. Myelosuppression was severe with a median nadir of neutropenia of 0.2 x 10(9) cells 1-1. However, 74% of the patient group received all six courses of chemotherapy and only 16 courses (7%) were delayed because of toxicity. There were three deaths associated with treatment-related neutropenia. The median survival of the total group was 14 months, with an actuarial 2 year survival of 37% and a minimum follow-up of 18 months. [A recent analysis, March 1989, demonstrated a 33%, 2 year actual survival.]
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PMID:Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for 'limited' stage small cell carcinoma of the bronchus. 255 90

The combination of carboplatin and etoposide is an active and well-tolerated regimen in the treatment of small cell lung cancer (SCLC). The aim of the study was to confirm whether the efficacy could be maintained if etoposide was administered orally. 106 consecutive, unselected, and untreated patients with SCLC (limited disease (LD) 44; extensive disease (ED) 62) were treated with a combination of carboplatin 300 mg/m2 intravenously (i.v.) day 1 and etoposide 240 mg/m2 orally days 1-3 every 4 weeks for six courses or until progression. If oral treatment was inconvenient, i.v. etoposide (120 mg/m2 days 1-3) was allowed. Thoracic irradiation (45 Gy in 22 fractions, split course) was given after three courses of chemotherapy to 29 patients with LD. Objective response (complete and partial) was seen in 89% (confidence interval (CI) 75-97) of patients with LD and in 53% (CI 40-66) with ED. Complete response was seen in 41% (CI 26-57) of patients with LD and in 8% (CI 2-18) with ED. Median time to progression for responders was 11 months and 6 months for patients with LD and ED, respectively. Corresponding median survival was 15 months (range 1-45 months) and 8.5 months (0-26 months). Myelosuppression comprised the main toxicity. Leucopenia (WHO III-IV) was observed in 20% and thrombocytopenia (WHO III-IV) in 16% of the cases. One patient died of sepsis during leucopenia. Oral treatment was convenient for most patients and therapy well tolerated. However, 9 patients (20%; CI 9-36%) with LD and 26 patients (42%; CI 29-56%) with ED received at least part of the etoposide treatment i.v.. The present study shows that the combination of carboplatin and oral etoposide is active and well tolerated, and may be used on an outpatient basis in patients with small cell lung cancer.
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PMID:Is carboplatin and oral etoposide an effective and feasible regimen in patients with small cell lung cancer? 769 81

A preclinical toxicology study of intraperitoneally administered liposome encapsulated doxorubicin and free doxorubicin was carried out in beagle dogs. Dogs received single intraperitoneal infusions of 1.5 mg free or 1.5, 2.25 or 3.37 mg liposomal doxorubicin/kg. One group of four dogs received 1.5 mg liposomal doxorubicin/kg every three weeks for 4 cycles. The dose limiting toxicity of free or liposomal doxorubicin given by the intraperitoneal route was a dose-related chemical peritonitis. This toxicity was more severe in dogs that received by the intraperitoneal route the previously determined maximally tolerated intravenous dose of liposomal doxorubicin (2.25 mg/kg). The abdominal toxicity was characterized by capsular fibrosis and ascites formation. Abdominal toxicity was life threatening after single doses of 3.37 mg liposomal doxorubicin kg, or after multiple (4) doses of 1.5 mg liposomal doxorubicin/kg. Thoracic toxicity (increased fluid, mediastinal edema, thickening of the parietal pleura) was seen after multiple (every 3 weeks for 4 cycles) intraperitoneal doses of 1.5 mg or single doses of 3.37 mg liposomal doxorubicin/kg. Myelosuppression was seen in all groups, but was less severe after intraperitoneal dosage than after intravenous dosage of liposomal doxorubicin.
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PMID:Preclinical toxicology study of liposome encapsulated doxorubicin (TLC D-99) given intraperitoneally to dogs. 777 49

Combination ifosfamide/carboplatin/etoposide (ICE) chemotherapy and ICE plus mid-cycle vincristine (VICE) are reviewed. Thoracic radiotherapy and prophylactic cranial irradiation given as single fractions in the majority of patients have been intercalated with VICE in the later studies. The patient populations have not been intensively staged with computed tomography, etc, but do have reasonable Karnofsky performance status ratings and biochemical screens. A policy of no dose reduction over six courses of VICE chemotherapy has been followed in three consecutive studies of 166 patients. The minimum length of follow-up is 26 months and the 2-year survival rate is > or = 30%. Hematopoietic growth factor support in an attempt to overcome the considerable myelosuppression with VICE therapy is currently being evaluated.
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PMID:Intensive combined-modality therapy in small cell lung cancer. 805 79

Lung cancer is one of the most common cancers and its associated mortality continues to rise in Japan. The lung cancer cure rate is still very low. To improve the survival of patients with lung cancer, well-designed and well-conducted clinical trials are essential. Several Japanese study groups have been conducting clinical trials for lung cancer. However, most randomized phase III studies were conducted by the Japan Clinical Oncology Group (JCOG), the West Japan Thoracic Oncology Group, and pharmaceutical companies supporting temporarily organized groups. In the past decade, the quality of Japanese clinical studies has improved tremendously. The results of JCOG9511 have recently been reported; and demonstrated that treatment with irinotecan/cisplatin significantly improved patient survival in extensive-stage small-cell lung cancer over standard etoposide/cisplatin, with less myelosuppression. A randomized phase II study using gefitinib (ZD1839; Iressa) for non-small-cell lung cancer was also recently reported and showed a high response rate against platinum-refractory lung cancer, especially in adenocarcinoma and in females. A 4-arm multicenter, randomized cooperative phase III study for advanced non-small-cell lung cancer is currently underway.
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PMID:Results of recent Japanese clinical trials in lung cancer. 1466 31