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)

In a phase II study, patients with locally advanced squamous cell carcinoma of the head and neck were treated with simultaneous chemoradiotherapy. Treatment was divided into three courses. Chemotherapy consisted of cis-diamminedichloroplatinum (II) (cisplatin [cis-DDP]) 60 mg/m2 intravenously (IV), fluorouracil (5-FUra) 350 mg/m2 IV, and folinic acid (leucovorin calcium [FA]) 50 mg/m2 IV on day 2 as bolus, and 5-FUra 350 mg/m2 over 24 hours and FA 100 mg/m2 over 24 hours on days 2 through 5. Radiotherapy consisted of 23.4 Gy over nine days divided into 13 fractions of 1.8 Gy each 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 over 51 days. Between August 1984 and October 1986, 62 (modified AJCC stage III, four; IV A, eight; IV B, 50) consecutive patients were entered in the study. Three patients died during treatment due to tumor hemorrhage. Of 59 patients, 48 (81%) achieved a clinically complete response (cCR); 11 (19%) achieved a partial response (cPR). Mean follow-up of the surviving patients was 29+ (24 to 44) months. Actuarial 2-year survival probability is 52%, including three early deaths from tumor bleeding. Tumor and neck nodes control rates at 2 years were 92% for stage III and IV A patients and 65% for stage IV B patients. Patients with cCR had a significantly better 2-year tumor and neck nodes control probability compared with patients who achieved cPR after therapy (P less than .001). Six patients developed distant metastases. Overall toxicity was tolerable, mucositis particularly was not a limiting factor.
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PMID:Cisplatin, fluorouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: a phase II study. 278 93

Drug resistance is a major problem in chemotherapy of squamous cell head and neck cancers (SCHNC). Since glutathione (GSH) plays a crucial role in mediating tumor cell resistance against various toxic insults, GSH metabolism in SCHNC xenografts was investigated. Xenografts from lymph node metastases contained markedly higher GSH concentrations compared with those derived from the corresponding primary lesions. After subcurative chemotherapy with cisplatin (DDP), a significant increase of both GSH levels and gamma-glutamyltranspeptidase activity (gamma-GT) was gained in tumor HT1M. Tumor HT3M showed high concentrations of GSH and gamma-GT, although these latter concentrations did not increase following chemotherapy with DDP. These findings suggest a possible impact of GSH metabolism on both the formation of metastases and the phenomenon of drug resistance in SCHNC.
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PMID:Glutathione content and gamma-glutamyltranspeptidase activity in squamous cell head and neck cancer xenografts. 290 36

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

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

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

We studied the effects of anticancer agents on the inhibition of cell shedding from the surface of multicellular tumor spheroids (MTS). MTS were produced from 2 human tumor cell lines; one melanoma and the other squamous cell lung cancer, by using liquid overlay culture technique. The cell shedding from the melanoma MTS was approximately 10-fold higher than the squamous cell carcinoma MTS. In the melanoma MTS, all 3 drugs studied - vincristine (VCR), doxorubicin (ADR) and cisplatin (DDP)-inhibited cell shedding and the degree of inhibition of cell shedding was drug concentration related. In the squamous cell carcinoma MTS, VCR was as active in inhibiting cell shedding as in the melanoma MTS, but ADR and DDP were less efficacious. When effects on cell shedding were compared with those on cell lethality, VCR produced inhibition of cell shedding at much lower concentrations than those producing cell kill effects. ADR and DDP produced cell lethality as effective as, or more effective than, inhibition of cell shedding. These data seem to parallel known effects of these agents on cell kill and inhibition of metastases. MTS may serve as an in vitro model for the study of cell shedding and metastasis.
Invasion Metastasis 1987
PMID:Effects of anticancer agents on the shedding of cells from human multicellular tumor spheroids. 367 41

74 patients with disseminated non-seminomatous testicular cancer were randomly entered on a prospective sequential combination chemotherapy regimen with mandatory crossover, consisting of either vinblastine/bleomycin or adriamycin/cis-dichlorodiammineplatinum (II) (DDP) as initial therapy. Independent of the randomization the overall remission rate in 71 evaluable patients was 89% including 54% complete remissions. 35% of the patients remained disease-free at 2+ to 28+ months with a median of 12 months. By additional surgical removal of residual pulmonary metastases in two patients the complete remission rate was increased to 40/71 (56%), and the number of patients with no evidence of disease to 27/71 (38%). According to the life-table method the two-years survival rates were 63% for complete responders and 29% for all other patients, which was significantly lower. 53 patients (75%) were alive at 3 to 28 months with a median of 9 months. Additional advanced abdominal disease, initially elevated beta-HCG and LDH and extension of pulmonary disease were of significant negative influence on the prognosis. The evaluation of single chemotherapy courses revealed equal efficacy of both combinations. However, response to adriamycin/DDP occurred in 46% of the courses, when vinblastine/bleomycin had failed, while response to vinblastine/bleomycin occurred only in 21% of the courses when adriamycin/DDP had failed. Thus different patterns of cross-resistance between these alternative regimens may exist.
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PMID:[Sequential combination chemotherapy with vinblastine/bleomycin and adriamycin/cis-dichlorodiammineplatinum (II) in non-seminomatous testicular cancer. I. Results of a prospective randomized phase III-study with 71 patients with disseminated disease (stage IV) (author's transl)]. 616 Dec 73

A case of rhabdomyosarcoma of the urinary bladder in an 11-month-old boy is presented. The chief complaint was complete urinary retention and histological examination showed embryonal rhabdomyosarcoma of the bladder. Initially, he was treated with vincristine, actinomycin-D and radiation therapy. This therapy was not effective, and he was next treated with vincristine, bleomycin, and cis-DDP. This therapy was significantly effective, and the tumor became non-palpable on physical examination. After six courses he was discharged and maintenance chemotherapy was continued until the tumor relapsed 1 year later. Finally he died of dyspnea due to diffuse pulmonary metastases approximately 2 years after the first diagnosis. We herein discuss several points which affect the prognosis and the usefulness of chemotherapy, especially combination therapy with vincristine, bleomycin, and cis-DDP for recurrent cases.
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PMID:[Rhabdomyosarcoma of the bladder in a child: report of a case]. 620 68

Effects of a combination chemotherapy using cis-diamminedichloroplatinum (II) (DDP) and its antidote, sodium thiosulfate (STS), on metastatic lung tumour in rats were studied. Rats were given an upper hemibody infusion (UHI) of 15 mg/kg DDP immediately after occlusion of the abdominal aorta and i.v. administration of 1581 mg/kg STS (200-fold molar ratio to DDP) 10 min later. The aortic clamp was released at approximately 11 min after the beginning of UHI when a half volume of STS solution was infused. Antitumour and side effects in this group were compared with those in the respective control groups given 5 mg/kg DDP alone by UHI or by systemic administration. In the group given UHI of DDP (DDP-UHI) in combination with STS, there was a significantly better antitumour effect than seen in the group given DDP alone, as evaluated by the number of lung tumour nodules and survival time after inoculation of the transitional cell carcinoma into the lung. Nephrotoxicity, as assessed by increase in BUN levels, was completely avoided. Haematological toxicity effects assessed by decreases in WBC were slight but body-weight loss due to anorexia was severe.
Clin Exp Metastasis
PMID:Upper hemibody infusion of cis-diamminedichloroplatinum (II) followed by systemic antidote, sodium thiosulfate, for lung metastasis in rats. 654 4


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