Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is the most lethal cancer in the United States, with 143,000 deaths predicted for 1991. The cure rate is extremely low (approximately 13%), in part because the propensity for early spread precludes surgical cure in most patients. Thus, chemotherapy or other systemic therapies are the only way to improve the dismal results. Cisplatin is an active agent in small cell lung cancer (SCLC) and perhaps the most active agent in nonsmall cell lung cancer (NSCLC). The toxicities and inconvenience of cisplatin make it less than ideal for lung cancer therapy. Carboplatin was developed to provide a less toxic, more convenient alternative to cisplatin. The data presented in this review suggest that carboplatin may be substituted for cisplatin in the treatment of extensive-stage SCLC. In limited-stage SCLC, there are insufficient data to determine whether it should replace cisplatin when used simultaneously with chest irradiation and etoposide. It may be substituted for cisplatin in cycles not using irradiation. In NSCLC, carboplatin may be used alone or with etoposide for the palliative management of metastatic disease. Its role in earlier stages of NSCLC needs investigation.
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PMID:Clinical experiences with carboplatin (paraplatin) in lung cancer. 132 16

The high cure rate among young men with metastatic testicular germ cell tumors heightens the issue of late treatment toxicity. Conventional combination chemotherapy based on cisplatin can be expected to cure 85% to 90% of patients with metastatic disease; however the cost of this success includes severe treatment side effects, including irreversible renal damage and the risk of neurotoxicity and ototoxicity. Carboplatin was investigated as a replacement for cisplatin in the treatment of these tumors because of its reduced toxicity. The Royal Marsden Hospital pilot studies have included 76 patients treated for metastatic nonseminoma with the combination carboplatin/etoposide/bleomycin between 1984 and 1988. The median follow-up at time of analysis was 24 months. The complete remission rate was 95% and the overall cause-specific survival was 98.5%. Also, 33 patients treated with single-agent carboplatin for advanced metastatic seminoma were followed for a median of 36 months. The actuarial progression-free survival was 79%, and 91% of patients were alive and disease-free. The results of these studies indicate that carboplatin has activity equivalent to cisplatin in germ cell tumors of the testis and is less toxic.
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PMID:Use of carboplatin in germ cell tumors of the testis. 132 24

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.
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PMID:Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990. 142 85

34 patients with head and neck cancer were treated with carboplatin and radiation therapy. Eligibility criteria included stage IV biopsy-proven squamous cell carcinoma with measurable disease and no distant metastases, Karnofsky performance status score of 60 or greater, age 18 years or more, no previous radiation therapy and adequate hematological, renal, and hepatic function. There were 27 males and 7 females. Ages ranged from 44-70 years with a median of 57 years. Follow-up ranged from 11-34 months with a median of 21 months. Total tumor doses ranged from 50-55 Gy with additional boosts of 15-20 Gy. Carboplatin was given in a dose of 100 mg/m2 once weekly (26 patients) and 200 mg/m2 once every 2 weeks (8 patients), during the radiation therapy course in all 34 patients. Each dose of carboplatin preceded irradiation. 25 patients responded while 9 did not. There were 19 complete responses (CR) and 6 partial responses. 4/19 CR recurred and 5/9 non-responding patients died of disease. Mild to moderate nausea and vomiting were seen in 52.3% of patients and mucositis was seen in 61.8% of patients. Moderate to severe hematological toxicity was seen in 35.3% of patients. Response rates and toxicity we observed during this study clearly show that the combination of carboplatin and radiation therapy is effective and suitable for the treatment of patients with stage IV head and neck cancer.
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PMID:Carboplatin and radiation therapy for stage IV carcinoma of the head and neck. Preliminary results of a phase II study. 151 13

Twenty-seven metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received carboplatin 100 mg/m2/day x 3 intravenously (i.v.) plus etoposide 100 mg/m2/d x 3 i.v. repeated at 4-week intervals. There were five partial responses (18.5%), two minor responses, and 12 disease stabilizations. The dominant metastatic disease sites were soft tissue in three partially responding patients and visceral metastases in the two remaining responders. The median duration of response and time to progression were, respectively, 10 and 26 weeks. Major toxicity was myelosuppression with 85% of patients developing leukopenia; 48%, anemia; and 30%, thrombocytopenia. Carboplatin plus etoposide has shown antitumor activity in our group of pretreated patients. Based on the same schedule, a first-line carboplatin plus etoposide Phase II trial has been started.
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PMID:Phase II trial of carboplatin and etoposide activity in pretreated breast cancer patients. 155 6

Cisplatin has played a major role in the treatment of germ cell tumors. However, it causes renal damage, severe nausea and vomiting. It is also neurotoxic and ototoxic. Carboplatin is an analog of cisplatin which, does not cause renal damage at therapeutic doses. It is not neurotoxic or ototoxic and it produces less gastrointestinal toxicity than cisplatin. We used carboplatin alone as an initial chemotherapy in a 36-year-old man with stage IIB seminoma. Following left radical orchiectomy the patient received 4 courses of carboplatin chemotherapy. After the first course of chemotherapy, tumor markers (LDH, beta-HCG) returned to the normal range. After 4 courses, the size of the retroperitoneal metastases was significantly reduced. The toxicity of 4 courses of carboplatin chemotherapy was generally milder than that of cisplatin-based combination chemotherapies such as PVB or VAB-6. There were no episodes of septicemia, thrombocytopenic bleeding or renal deterioration. The patient did not suffer from alopecia, neuropathy, symptomatic hearing loss, severe nausea or vomiting. Nine months after the completion of carboplatin chemotherapy, the patient remains well and free from disease progression. This case strongly suggests that single agent carboplatin therapy could be an effective and less-toxic treatment for advanced seminoma.
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PMID:[A case of advanced seminoma treated effectively with single agent carboplatin therapy]. 156 62

A phase II multi-center study of carboplatin for cervical carcinoma was carried out in 22 institutes throughout Japan. The patients registered consisted of 40 women with 39 cervical carcinomas and an endometrial carcinoma, of whom 31 were evaluable. Carboplatin was administered intravenously every 4 weeks at a dose of 400 mg/m2, in cases with no prior therapies and/or P.S. 0-1, and 300 mg/m2 in cases with prior therapies and/or P.S. 2-3. The overall response rate of 31 evaluable cases was 19.4% with 2 cases of CR and 4 cases of PR. The response rates by histological classification were 18.5% (5/27) for squamous cell carcinoma and 25.0% (1/4) for adenocarcinoma. Response rates analysed by lesion sites were 12.5% for primary tumors, 30.0% for local lesions and 20.0% for metastases. The response rate among patients without prior therapies was 14.3%, while those for patients with prior radiotherapy and for prior radiotherapy and chemotherapy were 33.3% and 13.3%, respectively. Major adverse effects observed were nausea and/or vomiting (52.9%), anorexia (44.1%) and malaise (35.3%). Hematologically, thrombocytopenia, leukopenia and anemia were frequently observed (52.9%, 35.3% and 32.4%, respectively). As for renal toxicity, elevation of BUN (2.9%) or serum creatinine (2.9%) and the decrease of creatinine clearance (14.3%) were observed, but they were mild, and tolerable. These results suggest that carboplatin is one of the most useful drugs against cervical carcinoma.
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PMID:[Phase II study of carboplatin in cervical carcinoma]. 305 77

Carboplatin (CBDCA, Bristol-Meyers, New York) is a second generation platinum analog. Preclinical and phase I clinical studies have indicated a different spectrum of toxicity compared with the parent compound. In order to study the activity of carboplatin against cancer of the head and neck, 31 patients with recurrent or metastatic disease (30 squamous-cell and one adenoid cystic carcinoma) were treated with doses of 60 to 80 mg/m2 administered daily by intravenous (IV) bolus injections for five days, repeated at every 4- to 5-week intervals. In most cases, treatment was administered on an outpatient basis. Eight patients (26%; 95% confidence interval, 12% to 45%) had complete (CR) or partial responses (PR) with a median duration of 4.5 months. Moderate bone marrow suppression was the main toxicity. Mild nausea and vomiting was unusual and no neuro- or nephrotoxicity were seen. These preliminary data suggest that carboplatin has activity against advanced squamous-cell carcinoma of the head and neck comparable with the results reported with cisplatin alone in similar patient populations. The potential advantages over the parent compound relate to the absence of nephrotoxic effects and mild gastrointestinal toxicity which allows for outpatient treatment. Because carboplatin toxicity is directly dependent on its mechanism of renal excretion, particular attention should be given for its use in patients with impaired renal function or when combined with nephrotoxic agents. Similarly, because the dose limiting toxicity with this agent is primarily hematologic, its use in combination with other myelotoxic agents should be carefully undertaken. Further studies are indicated in order to define the spectrum of activity of the new generation platinum analogs in various tumors in humans.
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PMID:Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. 353 24

A 49-year-old female presented with a low abdominal tumor. Before operation, she had neither evidence of androgen excess nor abnormal tumor marker values, but US, CT and MRI findings strongly suggested the possibility of a malignant ovarian tumor. Her operative findings were as follows: a goose egg-sized main tumor in the low abdomen, with a walnut-sized tumor in the right side, which grew around the right ureter, causing right non-functional kidney. Pathological examination revealed her tumor was a very rare type of malignant Sertoli-Leidig cell tumor with pelvic lymph nodes metastases. Most patients with this disease usually have good prognoses, but with metastasis or recurrence, no therapy is as effective as in epithelial ovarian cancer. In this case, we selected a new combination chemotherapy of CBDCA, Etoposide and Epirubicin, considering current changes in the chemotherapy for ovarian germ cell tumors and Sertoli-Leidig cell tumors of testis. Now, 1 year and 4 months after operation, she has no evidence of recurrence or metastasis. This study proposes a new, presumably more effective chemotherapy for an ovarian malignant Sertoli-Leidig cell tumor.
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PMID:[A case of ovarian malignant Sertoli-Leidig cell tumor treated with CBDCA, etoposide and epirubicin chemotherapy]. 757 20

Patients with brain metastases from small cell lung cancer (SCLC) have a poor prognosis. Although most patients die from metastatic disease outside the central nervous system, this disabling metastatic site often needs treatment to mitigate the signs and symptoms of intracranial disease. The effect of carboplatin (400 mg/m2 every 4 weeks) as second line treatment for recurrent or progressive brain metastases was studied in 20 SCLC patients. 19 patients could be evaluated: 16 by contrast enhanced brain computer tomography (CT) scan (2 patients had complete response, 6 partial response, 4 stable disease and 4 progressive disease) and 3 patients clinically, who had progressive disease. The objective response rate in the brain was 40% (95% CI:22-61%). The median response duration was 8 weeks (range 2-29). The median survival was 15 weeks (range 1-44). Previous cranial irradiation appeared to be beneficial for survival. There was only mild haematological and gastrointestinal toxicity. Carboplatin has activity against brain metastases and gives palliation in responding patients.
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PMID:Carboplatin as second line treatment for recurrent or progressive brain metastases from small cell lung cancer. 769 Nov 16


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