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)

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.
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PMID:Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin. 318 28

An in vitro chemosensitivity test, the succinate dehydrogenase inhibition (SDI) test, was used to examine 16 pairs of samples obtained simultaneously from primary and metastatic lesions of clinical gastric cancer. Concerning the metastases, 11 were in the lymph nodes and five in the liver. The chemosensitivities of metastatic lesions against six anti-tumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), and 5-fluorouracil (5-FU), differed from those in the primary lesions, and there were no correlations of chemosensitivities between the primary and the metastatic lesions against these drugs, except for DDP. The lymph nodes were more sensitive to CQ, ADM, MMC, DDP, ACR and 5-FU, while the liver was less sensitive than the primary lesions to CQ, ADM, MMC, DDP, and ACR. Our findings indicate that in patients with lymph node metastasis, there is a sensitivity to anti-tumour drugs, while in cases of liver metastasis, drug treatment may be less effective. We propose that chemosensitivity testing should be done when attempting to design anti-tumour drugs.
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PMID:Chemosensitivity differences between primary and metastatic lesions of clinical gastric cancer. 319 5

We added high-dose oral leucovorin to the combination of cisplatin and fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50 mg/m2, was administered at the start of cisplatin and every six hours throughout the duration of the 5-FU infusion. The dose of 5-FU was escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a second phase of the study, the dose of leucovorin was escalated to 50 mg/m2 every four hours. A total of 25 patients were registered: 23 had recurrent disease after extensive prior treatment; and two had newly diagnosed metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d with leucovorin administered every six hours. Toxicities at that level included mild to moderate myelosuppression and dose-limiting mucositis in the previously irradiated field. Identical toxicities were observed when administering 800 mg/m2/d of 5-FU with leucovorin every four hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who received prior cisplatin and 5-FU as induction chemotherapy); and eight patients failed to respond. The mean peak and trough plasma leucovorin concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L with administration of the drug every six hours, and 2.75 (+/- 2.15) mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours. We conclude that the combination of cisplatin, 5-FU, and leucovorin has activity in the treatment of recurrent head and neck cancer. The maximally tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in previously irradiated sites being dose-limiting. Plasma leucovorin concentrations exceeding 1 mumol/L are achieved following oral administration of this drug.
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PMID:Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer. 325 29

Sixty untreated patients with advanced carcinoma of the head and neck (stages III = 11 and IV = 49) were treated simultaneously with three cycles of polychemotherapy and radiation. Chemotherapy consisted of cisplatinum (DDP) 60 mg/m2 after prehydration with saline and mannitol, 5-fluorouracil (5-FU) 350 mg/m2 and folinic acid (FA) 50 mg/m2 on day 2 as a bolus and a continuous infusion of 5-FU 350 mg/m2/24 h and folinic acid (FA) 100 mg/m2/24 h from day 2-5. Concomitantly, accelerated hyperfractionated radiation was administered from day 3-11. Two fractions per day with 1.8 Gy each were given, 13 fractions in 9 days. This cycle was repeated two times on day 22 and 44 with an interval without treatment from day 16-21 and 34-43. Total radiation dose was 70.2 Gy in 51 days. Acute toxicities (WHO grade II and III) consisted mainly of leucopenia (75%), thrombopenia (15%), weight loss (mean 5.8 +/- 3.7%) and mucositis (66%). Grade IV was never reached. Except for 3 patients, who died during treatment due to fatal tumor bleeding or carotid rupture, all were able to finish the treatment with reduction in chemotherapy in only 95% (DDP) and 98% (5-FU) with no changes in the radiation protocol. Evaluation of tumor response at 3 months after end of treatment showed 68% complete and 32% partial responses. 5 patients developed distant metastases. Survival with local control after 12 months was 80.8% and 71.3% after 24 months. 1 and 2 years disease-free survival was 70.8% and 62.1%. Total survival irrespective of cause of death was 77.9% and 57.2% after 1 and 2 years. This particular simultaneous radio-polychemotherapy protocol appears to be well tolerable and highly effective in terms of tumor control and survival of advanced stages of head and neck cancer.
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PMID:[Results of simultaneous radio-polychemotherapy in advanced inoperable cancer of the head and neck]. 326 83

The tumor was found in the peritoneum of a 6-months old female NMRI-mouse. Histologically it can probably be classified as a less-differentiated reticulum-cell sarcoma (histiocytic sarcoma). Following ip. or sc. transplantation metastases were only in some cases found. After im. inoculation of tumor brei lungs, livers, kidneys, spleens and lymph nodes were free of metastases, as a bioassay revealed. The im. transplantation was the most suitable technique for chemotherapeutic experiments: It resulted in a 100% take rate and a relatively narrow and well reproducible death range; tumor size and life span of the animals could be used as therapeutic parameters. The tumor was highly sensible against the cytostatic drugs Cyclophosphamide, Doxorubicin and Vincristine. A moderate activity showed CCNU, Cis-DDP and Bleomycin, while DTIC and a novel Benzochinonguanylhydrazon-derivative only reversibly influenced the tumor growth and not the life time of the animals. Liposomally encapsulated Daunorubicin and Bleomycin had in general similar effectiveness as the drugs in its free form. Because of its high sensitivity against a lot of cytostatics with different mechanisms of action the tumor can be recommended for the screening of novel antineoplastic substances.
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PMID:Characterization of a new tumor in NMRI-mice suitable for chemotherapeutic experiments. 329 88

Surgical treatment is the most effective therapy for esophageal carcinoma, and adjuvant radiotherapy and chemotherapy are essential for the improvement of postoperative curability. The recurrence of carcinoma after curative surgery is often observed in the upper mediastinum and cervical portion. Fifty Gy of postoperative prophylactic irradiation has been given routinely and this has suppressed the local recurrence of the disease to a remarkable degree. Metastasis of carcinoma to internal organs was not controlled by radiotherapy. This occurs in the case of undifferentiated carcinoma, severe lymph node metastasis and positive invasion to vessels. Cisplatin, vindesine and bleomycin (DVB) combination chemotherapy and another cisplatin-based chemotherapy have been adapted for postoperative cases such as those in stages II, III and IV with radiotherapy. Cases of stage 0 and I with positive carcinomatous invasion to vessels have been treated reasonably with anti-cancer agents. Before chemotherapy, the anti-cancer activities of the drugs in subrenal capsule assay (SRCA) are tested using resected tumors and prospective clinical trials are being performed.
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PMID:[Clinical evaluation of adjuvant radiotherapy and chemotherapy for esophageal carcinoma]. 338 34

Thirty-four (6 stage III, 28 stage IV) patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneous radio-chemotherapy. Treatment was divided into three cycles. Chemotherapy consisted of cis-diamminedichloroplatinum(II) (cis-DDP) 60 mg/sqm i.v., 5-fluorouracil (5-FU) 350 mg/sqm i.v. and folinic acid (FA)-50 mg/sqm i.v. on day 2 and 5-FU 350 mg/sqm per 24 h and FA 100 mg/sqm/24 h on days 2-5. Radiotherapy consisted of 23.4 Gy/9 days divided in 13 fractions of 1.8 Gy delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy/51 days. Mean follow-up of surviving patients was 21 (14-34) months. 28/32 patients achieved complete response, 4/32 partial response. Actuarial one and two years survival were 88 and 58% including two early deaths from tumour bleeding. Local control rates at one and two years were 87 and 81%, respectively. This protocol produces excellent palliation and the chance of improved long term tumour control. Two patients developed distant metastases. Overall toxicity was tolerable. Since the treatment breaks were inserted after low radiation doses, acute mucositis healed rapidly and was not a limiting factor.
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PMID:Accelerated split-course radiotherapy and simultaneous cis-dichlorodiammine-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement for unresectable carcinoma of the head and neck. 344 4

Cisplatin was used in 14 bone and soft tissue sarcomas. Severe vomiting developed in all cases, but the duration was relatively short. Renal function was disturbed in cases with a higher total dose. This side effect was considered to be the dose-limiting factor of cisplatin. Seven cases showed high-frequency deafness but they did not complain of disturbance during conversation. In seven metastatic osteosarcomas, one was evaluated as a partial response and one as a minor response. No response was observed among three soft tissue sarcomas. Three cases of osteosarcoma receiving cisplatin in adjuvant chemotherapy have been disease-free for 4 and 46 months after resection of pulmonary metastases and for 50 months after resection of the primary tumor. We consider cisplatin to be the first-choice drug in cases resistant to adriamycin or methotrexate, but there are some problems when cisplatin is used in adjuvant chemotherapy, because of its side effects.
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PMID:[Chemotherapy using cisplatin in bone and soft tissue sarcoma]. 346 52

A phase II group study of cisplatin for cervical and endometrial carcinomas was carried out in 19 institutes throughout Japan. The patients entered consisted of 62 women with cervical and 7 with endometrial carcinoma of whom 39 and 4 were evaluable, respectively. Cisplatin was administered in either of two regimens; 10-20 mg/m2 i.v., on days 1-5, or 50-100 mg/m2 i.v., on day 1, every 3 to 4 weeks. The responders comprised 4 CRs and 10 PRs for cervical carcinoma and 1 CR and 2 PRs for endometrial carcinoma, and the response rates were 35.9% and 75.0%, respectively. The response rates by histological classification were 39.4% (13/33) for squamous cell carcinoma and 16.7% (1/6) for non-squamous cell carcinoma. Response rates analysed by lesion site were 33.3% for primary tumors, 36.8% for local lesions and 33.3% for metastases. Furthermore, the response rate among patients without any prior chemotherapy was 44.4% vs. 16.7% for those with prior chemotherapy. Adverse effects included nausea and vomiting (95.3%), anorexia (93%), anemia (72.1%), leucopenia (60.5%) and elevation of BUN (16.3%). Adverse effects were tolerable. We concluded from these results that cisplatin is among the most efficacious and useful drugs against cervical (and endometrial) carcinoma(s).
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PMID:[Phase II study of cisplatin in cervical and endometrial carcinomas]. 356 7

Cisplatin (25 to 120 mg. per m.2) was injected into the internal iliac arteries of 33 patients with locally advanced bladder cancer. Of the patients 9 were inevaluable for response to the cisplatin, since they began radiotherapy to the bladder before course 2 of cisplatin as part of a preplanned therapeutic approach. One patient received the treatment as postoperative adjuvant therapy, 1 did not return for followup and 1 with metastatic disease did not undergo repeat cystoscopy. Of 21 evaluable patients 3 (14 per cent) achieved complete remission, 12 (57 per cent) achieved partial remission, 2 (14 per cent) were stable and 4 (19 per cent) failed. The response rate was higher in patients receiving 100 to 120 mg. per m.2 per course than in patients receiving lower doses (all except 1 of whom received 60 or less mg. per m.2 per course) (86 versus 64 per cent) and it was higher in patients without prior radiotherapy or chemotherapy. The response rate in patients with previously untreated invasive transitional cell carcinoma was 88 per cent. Of the 33 patients 21 were alive at last followup, with a median duration of followup of 32 weeks. Toxicity was dose-related and local neurotoxicity was excessive at cisplatin doses of 100 to 120 mg. per m.2. Diabetic patients were particularly prone to have neurotoxicity. Other toxicity generally was not severe and consisted of ototoxicity, nephrotoxicity, myelosuppression, nausea, vomiting and diarrhea. Even elderly patients and patients with cardiac disease tolerated the treatment well. We plan to proceed with further intra-arterial cisplatin studies in which all patients except those more than 80 years old will be treated with an intra-arterial cisplatin dose of 90 mg. per m.2 per course combined with radiotherapy with or without cystectomy.
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PMID:Intra-arterial cisplatin for bladder cancer. 359 43


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