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

Previous experience using 131I anti-CEA antibody, which irradiates at a variable low dose rate in combination with a multimodality treatment program, has demonstrated acceptable toxicity and response in primary intrahepatic cholangiocarcinoma. In attempting to improve therapy, Cis-platin was added to the prior regimen. Induction therapy was unchanged. One month later, chemotherapy was given (doxorubicin, 15 mg, 5-fluorouracil, 500 mg, plus Cis-platin, 20 mg/M2) followed the next day by outpatient administration of 20 mCi 131I anti-CEA by i.v. bolus. Five days later, 10 mCi was administered. The latter regimen (chemotherapy plus 20 + 10 mCi 131I anti-CEA) was repeated every 2 months using polyclonal antibodies derived from different species (rabbit, pig, baboon, and horse). Twenty-four patients (29% with prior chemotherapy and/or metastases) were prospectively treated according to this regimen. Toxicity was limited to hematologic toxicity and was manifested by thrombocytopenia and leukopenia (17% and 4% grade 4, respectively, according to RTOG toxicity criteria). Tumor remission was evaluated by CT volumetric analysis and demonstrated a 14% response rate for the induction portion of therapy, 24% for the radioimmunoglobulin portion of treatment, and 50% remission rate when all subsequent tumor volumes were compared to the pre-treatment volume (entire program). The median survival for the entire group of patients was 10.1 months. This result is superior to previously reported trials and, in comparison to our previous study (10.1 vs 6.5 months median survival), further advancement in protocol design appears to have been made. In view of the rarity of this disorder, a randomized trial is not possible and strict statistical analyses cannot be made. The mechanism of 131I-anti-CEA variable low dose irradiation and chemotherapy interaction is discussed as well as further potential modifications for treatment improvement.
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PMID:Variable low dose rate irradiation (131I-anti-CEA) and integrated low dose chemotherapy in the treatment of nonresectable primary intrahepatic cholangiocarcinoma. 165 45

A case of metachronous lung metastasis treated by the combination therapy of Etoposide, Epiadriamycin and CDDP (modified EAP) is reported. A 47-year-old female who had undergone standard radical mastectomy for left. breast cancer was shown to have multiple metastases to the right. lung two years and seven months after surgery. The metastatic lesions disappeared after six series of modified EAP (VP 16 450 mg + ADR 40 mg + CDDP 100 mg/body) x 6 in seven months. Major side effects such as leukopenia and thrombocytopenia were not observed during the course. No recurrence had been noted for 14 months since the disappearance of the metastatic lesions. It is thus emphasized that the effect of EAP may be expected for the treatment of breast cancer.
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PMID:[Remarkable effect of the combination therapy of etoposide, epiadriamycin, and CDDP (EAP) in the treatment of metachronous lung metastases of breast cancer--a case report]. 165 28

Thirty-six patients with advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with a regimen including cisplatinum (CP) 30 mg/m2 i.v., 5-fluorouracil (5-FU) 500 mg/m2 i.v. bolus, folinic acid (FA) 200 mg/m2 i.v. in a continuous one-hour infusion, and bleomycin (B) 15 mg i.m. on the first and second days and repeated every 28 days. Thirty-three patients (25 with recurrent disease and 8 untreated) are evaluable for objective response. Of these, 4 (12%) achieved CR and 15 (45%) PR. All of the untreated patients responded. The mean duration of response in the patients with recurrent or metastatic disease was 5.5 months (range 2-10+). Remission of symptoms, such as pain and dysphagia, was obtained in 58% and in 44%, respectively. Subjective remission occurred almost exclusively in objectively responsive patients. The major side effects were leukopenia (55%) and nausea/vomiting (58%). This regimen is active in the treatment of advanced SCCHN. The quality of life may be improved in responsive patients.
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PMID:5-fluorouracil + folinic acid with cisplatinum and bleomycin in the treatment of advanced head and neck squamous cell carcinoma. 172 18

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.
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PMID:Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma. 174 82

We conducted these experiments to investigate the differences between continuous portal and one shot portal infusion of 5-fluorouracil (5-FU) using male Donryu rats. Continuous portal infusion of 5-FU (20 mg/kg/day x 5 days) revealed no remarkable side effects on the rats with significant decrease in the number of liver metastases generated by intraportal inoculation of ascites hepatoma AH60C. Consecutive 5-day administration of 5-FU (20 mg/kg x 5) by one shot method via spleen resulted in no metastases but caused death in 75% of rats because of severe leukopenia and dehydration. The rats receiving one shot infusion of 5-FU (33.3 mg/kg x 3, day 1, 3, 5) via spleen showed a significant decrease in the number of metastases without lethal side effects. Continuous portal infusion of 5-FU would be a safe and effective therapy to prevent liver metastases, whereas one shot portal infusion of 5-FU may give rise to severe side effects while preventing liver metastases.
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PMID:[An experimental study on portal infusion of 5-fluorouracil]. 187 31

The antitumor activity of carboplatin (400 mg/m2 intravenously every 4 weeks) in advanced breast cancer was evaluated in two consecutive trials enrolling patients with and without prior exposure to chemotherapy, respectively. All patients had measurable disease in at least one site. The first trial included patients who had received prior chemotherapy (adjuvant, neoadjuvant, or chemotherapy for metastatic disease). All but one of these patients had previously received doxorubicin-containing combinations. There were no objective responses among the first 14 evaluable patients, although 7 of them had stable disease, including 2 with minor responses. The second trial, carried out with patients who had no prior exposure to chemotherapy, is ongoing. Currently, 6 of 19 evaluable patients have obtained a complete (1) or partial (5) response to carboplatin, resulting in an overall response rate of 32%. In both studies, toxicity was mild, mainly consisting of emesis (88%), leukopenia (22%), and thrombocytopenia (12%). Thus, by standard criteria, carboplatin was not found to be active in breast cancer patients with prior exposure to chemotherapy. Preliminary results in patients without such exposure are encouraging, although additional patients are needed to confirm these data.
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PMID:Phase II study of carboplatin in advanced breast cancer: preliminary results. 199 32

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.
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PMID:Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study. 199 44

Twenty-four patients with advanced metastatic cancer were treated with continuous intravenous 5-fluorouracil infusion 200-300 mg/m2/day and alpha interferon 3 million units subcutaneously 3 times per week. The average duration of treatment was 87 days (range 22-204 days). 5-fluorouracil could be infused 66% of the planned time on treatment, and patients received an average of 60% of the planned interferon injections. Objective tumor responses were seen in 6 of 17 previously untreated patients (35%). Twenty-two of the 24 patients (92%) experienced toxicity (greater than or equal to ECOG grade II) that required treatment interruption and subsequent dose reduction predominantly for the following reasons: mucositis (67%), hand-foot syndrome (21%), and leukopenia (25%). The incidence of treatment limiting toxicity is higher than previously observed with 5-fluorouracil infusion alone. This suggests true augmentation of 5-fluorouracil effect by interferon. 5-Fluorouracil infusion and alpha interferon is a potentially useful combination that needs further evaluation in future phase II and phase III trials.
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PMID:Continuous 5-fluorouracil infusion and alpha interferon in advanced cancers: a report of initial treatment results. 201 9

A total of 60 patients with advanced breast cancer were treated with a combination of prednimustine (P: 110 mg/m2, days 1-5), mitoxantrone (M: 12 mg/m2, day 1) and 5-fluorouracil (F: 500 mg/m2, day 1) (PMF). Treatment was repeated every 3 weeks. In all 53 patients were evaluable for response. A total of 12 subjects had failed prior chemotherapy for metastatic disease. In response to PMF treatment we observed 21 partial remissions and 3 complete remissions, amounting to a total response rate of 45%. The median duration of response was 39 weeks, and median survival was 56 weeks. Dose-limiting side effects were leukopenia (40 cases) and thrombocytopenia (11 patients). Nausea and vomiting was experienced by 93% of subjects; in 56% of cases it reached WHO stage II-III. Alopecia occurred in 18% of our patients. Our results suggest that PMF represents an active regimen in the treatment of advanced breast cancer and yields a response rate of 45%. Considering that the majority of our patients had not received prior chemotherapy, the question remains open as to whether a 45% response rate outweighs the observed toxicity.
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PMID:Prednimustine combined with mitoxantrone and 5-fluorouracil for first and second-line chemotherapy in advanced breast cancer. 201 18

The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were less than or equal to 70 years of age and had a Karnofsky performance status of greater than or equal to 50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m2 ifosfamide given i.v. on days 1-5, 120 mg/m2 etoposide given i.v. on days 1-3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2-8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n = 37), grades 3/4 thrombocytopenia (n = 12), and grades 2/3 anemia (n = 13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n = 2) and 8 (n = 1) months for CR and 2 (n = 2), 6 (n = 2), and 10 (n = 1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting.
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PMID:Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer. 211 56


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