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)

Thirty-five patients with bulky (designated as > or = 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m2, and vincristine, 1 mg/m2, administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulocytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management.
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PMID:Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study. 777 47

Combination chemotherapy with 5-FU and CDDP was given to two patients with far advanced gastric cancer. One patient was associated with metastases of lung, liver, pancreas and Virchow and periaortic lymph nodes, and the other was associated with metastases of periaortic lymph nodes and malignant ascitis. The regimen consisted of 5-FU 1,000 mg/m2 (day 1-5, continuous infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to the 21st day. The response to chemotherapy showed shrinking of primary gastric lesions and metastases of liver, pancreas and periaortic lymph nodes, and disappearance of Virchow lymph nodes and malignant ascitis. Adverse reactions were thrombocytopenia (Grade 4), leukocytopenia (Grade 3), stomatitis (Grade 1, 3), vomiting (Grade 1, 2) and peripheral neuropathy (Grade 3). This therapy is thought to be effective against far advanced gastric cancer.
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PMID:[Two patients with far advanced gastric cancer responding to combination chemotherapy with 5-FU and CDDP]. 782 65

Phase II clinical trials of single-agent paclitaxel have demonstrated the drug's activity in ovarian cancer, breast cancer, and both small cell and non-small cell lung cancer. A recently completed trial in recurrent head and neck cancerpatients conducted by the Eastern Cooperative Oncology Group resulted in a 40% (12 of 30) overall (complete plus partial) response rate with a high dose of paclitaxel (250 mg/m2 by 24-hour continuous infusion) and granulocyte colony-stimulating factor support. Responses were observed in previously irradiated sites of locoregional disease as well as in distant metastases. The major toxicities were brief grade 3-4 neutropenia occurring in 91%, peripheral neuropathy in 39%, and arthralgias/myalgias in 39% of treated patients. Confirmatory single-agent trials with paclitaxel are in progress in the United States and Europe. Phase I and II trials also in progress or planned combine paclitaxel with cisplatin or carboplatin; ifosfamide; methotrexate; and cisplatin/5-fluorouracil. Lower doses (135 to 175 mg/m2) and alternative infusion schedules ranging from 3 hours to 10 days are also under evaluation in head and neck cancer and other solid tumors. Studies combining paclitaxel and radiotherapy are reviewed as well.
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PMID:Current and future trials of Taxol (paclitaxel) in head and neck cancer. 786 35

Taxol is the first of the taxanes, a new class of cytotoxic agents whose cellular target is the microtubules network. Taxol induces the polymerisation of the alpha and beta sub-units of the tubulin. This mechanism of action which is different from the vinca-alkaloids explains the main cytotoxic activity of paclitaxel through the formation of abnormal and stable bundles of microtubules. Severe hypersensitivity reactions which were seen in early phase I studies are prevented by an oral corticosteroids and H1 and H2 blockers premedication. Profound neutropenia is frequent but of short duration explaining that infectious manifestations are rare and neutropenia not cumulative. Thrombopenia and anemia are rare. Neurotoxicity is dose related but severe peripheral neuropathy is rare. Conduction abnormalities are mainly asymptomatic bradycardias. In second line ovarian cancer and breast metastatic cancer a noticeable level of activity has been observed, and in lung and head and neck cancer Taxol has proved to be effective.
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PMID:[Taxol (paclitaxel), first molecule of a new class of cytotoxic agents: taxanes]. 789 25

The Eastern Cooperative Oncology Group (ECOG) is conducting a phase II trial of Taxol in patients with histologically confirmed, advanced squamous cell carcinoma of the head and neck. Patients entered in the study to date either had recurrent disease or were newly diagnosed with incurable local-regional disease or distant metastases. Prior chemotherapy was limited to induction or adjuvant chemotherapy at least 12 months prior to entry in the study. All patients had an ECOG performance status of 0 or 1 and measurable disease. The treatment schedule was Taxol 250 mg/m2 by 24-hour continuous intravenous infusion followed by r-met Hu granulocyte-colony stimulating factor 5 micrograms/kg/day subcutaneous injection day 3 to 15 or until the absolute neutrophil count was greater than 1500. Cycles were repeated every 3 weeks. As of September 1, 1992, 27 patients were registered in the study. Of these, three patients were determined to be ineligible, and three were too early to evaluate. There were two early deaths, one definitely and one possibly drug related. Two complete and five partial responses have been observed. Twenty-three patients receiving 83 courses were evaluable for toxicity. Myelosuppression was the primary toxicity observed with 17 (74%) patients experiencing grade 3 or 4 leukopenia and with 20 (87%) patients experiencing grade 3 or 4 neutropenia lasting an average of 2 days (range, 1-4). Peripheral neuropathy occurred in nine patients (grade 1, five patients; grade 2, three patients; grade 3, one patient). Other infrequent toxicities were stomatitis, nausea and vomiting, and myalgias. This trial will continue until 30 eligible patients are accrued.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II evaluation of Taxol in advanced head and neck cancer: an Eastern Cooperative Oncology group trial. 791 24

Fotemustine is a new nitrosourea derivative whose activity has been demonstrated on metastatic melanoma with specific activity on brain metastases and also on poor prognosis lung cancers. Results of in vitro studies of a cisplatin-fotemustine combination seem promising. In order to evaluate the efficacy and safety of this combination, we performed two trials. 6 patients entered a preliminary study whose schedule was cisplatin 120 mg/m2 on day 1 and fotemustine 100 mg/m2 on days 1 and 8. 22 patients were enrolled in a second study which added 120 mg/m2 cisplatin on day 22 followed by a 4-week rest period. In both trials, maintenance therapy consisted of cisplatin 100 mg/m2 and fotemustine 100 mg/m2 every 3 weeks until progression. Despite the poor prognostic factors which characterised our population (metastatic disease 86%, brain metastases 59%, < or = 80% performance status 45%), the results remain attractive with a 23% partial response rate (29% in non-pretreated patients). Moreover, 3 out of 8 patients with evaluable cerebral metastases achieved a partial response (37.5%). Toxicity was mild and related to the cumulative dose of cisplatin (peripheral neuropathy and renal toxicity). We concluded that these results need to be confirmed in a randomised trial.
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PMID:Cisplatin-fotemustine combination in inoperable non-small cell lung cancer: preliminary report of a French multicentre phase II trial. 808 Jun 71

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.
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PMID:Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor. 893 53

A patient who had a high-grade uterine leiomyosarcoma (LMS) with extensive intra-abdominal and pulmonary metastases at the time of diagnosis underwent supracervical hysterectomy, bilateral salpingo-oophorectomy and tumor reductive surgery. She then received induction chemotherapy with paclitaxel 135 mg/m2 over 24 h and carboplatin (target AUC = 7.5 mg.ml/min) monthly for seven courses, achieving remission with a small amount of residual disease. The treatment was well tolerated except for peripheral neuropathy. Accordingly, the combination of carboplatin and paclitaxel may be considered in patients with advanced high-grade LMS of the uterus, and this regimen warrants further study in this disease.
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PMID:Remission of advanced uterine leiomyosarcoma with pulmonary metastases with carboplatin and paclitaxel. 899 Nov 94

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.
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PMID:Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study. 904 28

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.
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PMID:Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. 913 91


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