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)

Twenty year's (1959-1979) experience in the treatment of osteosarcoma at the Bone Tumor Center of the Istituto Ortopedico Rizzoli is presented. During this period 433 cases were recorded, but only 266 were considered. All the patients underwent surgery but after 1970 whole-lung irradiation (1971), immunotherapy (1971), and chemotherapy (1972 onward) were added as adjuvant therapies on a nonrandomized basis. In the group treated with surgery alone the prognosis was very poor: 10% survived nine years or more after the diagnosis, an average disease-free interval of 7.7 months and an average survival time of 13 months. Monolateral whole-lung irradiation had negative results and was abandoned after six cases. Adjuvant immunotherapy with irradiated autologous tumor cells gave moderately positive results in 16 patients, but only by delaying the appearance of first metastases, therefore increasing the time of survival. Adjuvant chemotherapy was performed with three different protocols: one protocol with ADM only and two protocols using VCR + MTX (at medium dose) + ADM, administered according to two different schedules. Superimposable results were obtained with these three regimens. With equal follow-up, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly higher than that of patients treated with surgery alone (P less than 0.001). The patients in the chemotherapy group who had relapses showed a prolonged time (mean = 12.3 months) to the onset of the first metastasis. Adjuvant chemotherapy caused virtually no morbidity and no deaths. Reference is made to the advantages of a large and homogeneous caseload deriving from a single institution to avoid preselection bias and evaluate the effectiveness of new therapeutic approaches when patient randomization has not been employed.
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PMID:The treatment of osteosarcoma of the extremities: twenty year's experience at the Istituto Ortopedico Rizzoli. 694 43

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.
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PMID:High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity. 696 19

Forty-three patients, ranging in age from 7 to 30 years (median age, 17 yr), with primary osteogenic sarcoma (OS), confirmed by biopsies and with no evidence of metastatic disease at the time of diagnosis, received T-7 chemotherapy for an average of 4 months before surgery, including high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR) (median, 7 courses), and 1 course each of bleomycin, cyclophosphamide, and dactinomycin, and adriamycin. At the time of definitive surgery, the surgical specimen showed a good histologic response to chemotherapy (grade III or IV response) in 29 (67%) of 43 patients and a poor histologic response (grade I or II response) in 14 (33%) of 43 patients. Among those who responded well, no patient relapsed, as all received a complete course of preoperative and postoperative chemotherapy for more than 5 to over 28 months after the initiation of treatment (medium, 13 mo). Among those who responded poorly, 6 of 14 patients relapsed with pulmonary metastases (a thoracotomy was beneficial to 1), 4 of 6 patients are alive with disease, and 1 patient died of progressive disease. On retrospective analysis, we observed that good and poor responders did not differ in the distribution of sex, age, race, primary site of disease, or histologic subtype of OS. An elevated alkaline phosphatase level that returned to normal under preoperative chemotherapy indicated a good response. Neither the 24-, 48-, and 72-hour serum MTX levels nor the fluid intake and urinary output during 3 days that followed HDMTX with CFR correlated significantly with tumor response. Based on our studies with this form of therapy, we concluded that the response of OS to preoperative chemotherapy is of prognostic value.
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PMID:Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor). 697 39

Thirteen patients with inoperable squamous cell lung cancer were treated by a protocol combining multiple chemotherapy with radiotherapy. Chemotherapy with Adriamycine, Vinblastine, Cyclophamide, Methotrexate and Cis-platinum was administered every month, followed by two radiotherapy sessions with doses of mediastinum. Six cycles were programmed. In 11 non-metastatic patients, 8 responses were obtained (4 objective remissions). Three developed distant metastases. However, mean survival (27 weeks) and 1 year survival (2/10) rates were disappointing. Multiple chemotherapy could be useful in decreasing tumoral size before radiotherapy, modalities of combined treatment should be studied.
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PMID:[Sequential chemotherapy and radiotherapy in inoperable squamous cell lung cancer (author's transl)]. 701 22

A randomized prospective clinical trial involved 259 cases of advanced recurrent Stage III and IV epidermoid cancers of the head and neck. The cases were randomized among three treatment programs evaluating two dose schedules and a combination treatment of methotrexate. The treatments consisted of: weekly methotrexate, biweekly methotrexate with leucovorin rescue (ML), and biweekly ML combined with cyclophosphamide and cytosine arabinoside (MLCC). Equivalent overall drug-related toxicity was produced with a 5% drug-related fatality rate. Methotrexate alone produced significantly more skin and mucosal toxicity, and the combination (MLCC) resulted in more hematologic toxicity than other treatments. Complete and partial objective responses were achieved in 26%, 24%, and 18% by each treatment. Methotrexate alone produced a median duration of response and 105 days compared with 42 and 49 days from the other treatments. Duration of response was significantly longer and survival was better in the methotrexate-alone group. Response was markedly stage dependent; 40% of Stage III patients achieved response, whereas only 17% of Stage IV patients responded. Presence of visceral metastases decreased response rates and the likelihood of response was particularly compromised by pulmonary metastatic spread; only seven of 54 such patients responded. Decreased survival was related to non-ambulatory performance status, disease-free intervals of less than one year and weight loss. Survival differences between Stage III and IV patients could not be shown. This study demonstrates the therapeutic superiority of weekly i.v. treatment with methotrexate but failed to support claims of an improved therapeutic index for high-dose methotrexate with leucovorin rescue. As the only randomized prospective clinical trial of chemotherapy in advanced head and neck cancer, this study reinforces the weekly i.v. schedule of methotrexate as the standard against which other drug schedules and drug combinations should be compared.
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PMID:A randomized prospective comparison of intermittent methotrexate, methotrexate with leucovorin, and a methotrexate combination in head and neck cancer. 702 49

This report describes a novel method of immunochemotherapy; the active immunization to the drug 5-fluorouracil (5-FU) with enhanced antitumor activity resulting from its subsequent systemic administration. Two metastasizing carcinomas in the Fischer strain (F344) rat have been used: a chemically induced bladder carcinoma (FBCa) and a spontaneous mammary adenocarcinoma (MACa). Both tumors grow rapidly and result in 100% mortality within 10 wk of implantation. Neither tumor is sensitive to systemic 5-FU alone. Intradermal sensitization to 5-FU before FBCa tumor implantation, followed by 5-FU administered systemically, resulted in significant tumor regression and improvement in survival with eradication of all tumor and cure in 20% of animals. A similar antitumor effect was observed with the MACa. A comparable drug effect was observed when methotrexate sensitization was given before FBCa implantation followed by systemic MTX. Specificity to the sensitizing drug was demonstrated by the lack of effect of sensitization with either 5-FU or MTX unless followed by systemic therapy with the requisite sensitizing agent. Sensitization to 5-FU has also been assessed after FBCa implantation followed by resection of the local tumor. Resection was performed after distant tumor metastases had occurred, and was followed by systemic 5-FU therapy. Whereas tumor resection alone failed to cure any animal, sensitization to 5-FU increased cure rate fourfold over animals receiving systemic 5-FU alone. Antibody to 5-FU in the sera of sensitized animals has been suggested by an immunoenzymatic staining technique and its specificity confirmed in a radioimmunoassay. It is postulated that a combination of the systemic agent and the antibody elicited to it by sensitization produces the significant antitumor effect observed. The antitumor effect observed with this new approach to immunochemotherapy warrants further experimental and clinical study.
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PMID:Sensitization to low dose 5-fluorouracil. Subsequent enhancement of its systemic antitumor effect in the rat. 710 95

Forty patients with asymptomatic metastatic cancer to the liver discovered at the time of laparotomy were treated by combined intrahepatic arterial chemotherapy and internal irradiation in the form of 90Yttrium microspheres. One group of 25 patients were treated by a catheter inserted at the time of operation and received 100 mCi; of 90Yttrium microspheres and 5-fluorouracil on a continuing basis. They survived an average of 26 mo (varying from 9 to 60 mo). The second series of 15 patients referred after surgery were treated by the percutaneous insertion of the catheter into the hepatic artery and received a bolus of combined chemotherapy consisting of PlatinolTM, Methotrexate, and 5-fluorouracil. They survived an average of 31 mo, which varied from 12 to 60 mo. The dose of 100 mCi of 90Yttrium was well tolerated by the liver. Prospective studies are in progress, limiting the treatment to the internal irradiation to determine its precise role in the overall treatment of metastatic cancer to the liver.
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PMID:Treatment of asymptomatic metastatic cancer to the liver from primary colon and rectal cancer by the intraarterial administration of chemotherapy and radioactive isotopes. 720 Oct 51

Intraarterial chemotherapy using Methotrexate (MTX) was applied on 128 patients with carcinoma of the head and neck. If possible, the operation was performed followed by radiation, including cervical lymph nodes after initial chemotherapy. The aim of i.a. chemotherapy is to realise a partial remission of the tumor mass so that better conditions are available for the following operation respectively radiation. The 1 year NED results and the 3 year survival rate show an improvement in comparison with published results, including the regional lymph nodes metastases. This is especially the case when chemotherapy is followed by the operation and radiation. The tumor mass and in many cases the regional lymph nodes were reduced and subjective complaints were lessened. -- The additional i.a. chemotherapy with MTX seems to us justified, especially because of the low complication rate, although it is no substitute for radiation and surgery.
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PMID:[Intraarterial chemotherapy in carcinomas of the oral cavity, oro- and hypopharynx (author's transl)]. 721 90

182 patients with testicular tumors were treated since 1960. The best results from treatment of nonseminomatous germinative testicular tumors were obtained according to the following regimen: Stage A: (Tumor limited to the testis without invasion of the cord): Radical orchiectomy, lymphadenectomy, immune stimulation. Stage B1 (Invasion of the cord but less than 6 positive retroperitoneal lymph nodes): Additional triple chemotherapy with Actinomycin D, Chlorambucil and Methotrexate for 2 years. Stage B2 (More than 6 positive retroperitoneal lymph nodes): Additional radiotherapy with 4500 rads. Stage C (Distant metastases): Radical orchiectomy, retroperitoneal lymphadenectomy, immune stimulation, triple drug chemotherapy for 2 years with Actinomycin D, Methotrexate and Vincristine.
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PMID:[Treatment of testicular tumors]. 740 84

Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is most successful for patients who have had an antecedent molar pregnancy with a plateau or persistent beta-human chorionic gonadotropin elevation after molar evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has been associated with high cure rates, as has methotrexate with citrovorum factor rescue, which reduces toxicity. Standard definitions of low-risk gestational trophoblastic disease and response assessment are critical to a comparison of prognostic features related to single-agent therapy success. Methotrexate with folinic acid rescue administered as primary therapy does achieve an excellent therapeutic outcome with limited chemotherapy exposure but at increased cost. The weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is inexpensive and allows close monitoring of disease status. Single-dose or pulsed actinomycin-D provides a high level of complete response, although gastrointestinal toxicity, mainly nausea and vomiting, is quite common. Management of first-line chemotherapy failures is unclear, although in the GOG methotrexate trial it was evident that another agent, such as actinomycin-D, should be used to provide the highest success rate. The use of a single agent in low-risk metastatic trophoblastic disease (lung and/or vaginal metastases) depends upon restricting it to patients who have not failed prior chemotherapy, have a low World Health Organization score and have no evidence of the presence of choriocarcinoma, but a much higher first-line failure rate should be anticipated than in nonmetastatic disease. Other single-agent regimens have been proposed that are worthy of investigation to create a safer, more efficacious and more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of single-agent chemotherapy regimens for gestational trophoblastic disease. 751 17


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