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)

Useful palliation can often be achieved when standard treatment approaches of external beam irradiation and chemotherapy with or without resection are used for locally advanced primary rectal malignancies. Local control and long-term survival are achieved in only 10% to 50% of patients, however, due to the limited irradiation tolerance of surrounding organs and tissues. Encouraging trends exist in separate intra-operative irradiation analyses from Massachusetts General Hospital and Mayo Clinic with regard to improvement in local control and possibly survival of locally advanced rectal lesions, warranting continued evaluation of such approaches. Disease control within the intra-operative and external irradiation field is decreased, however, when the surgeon is unable to accomplish gross total resection. Therefore it seems reasonable to consistently add 5-Fluorouracil with or without Leucovorin during external irradiation and to evaluate the use of dose modifiers, such as sensitizers or hyperthermia, in conjunction with intra-operative irradiation. Since high systemic failure rates exist with both locally advanced primary and recurrent lesions, more effective chemotherapy needs to be evaluated during external irradiation as well as after completion of such. In view of survival advantages with 5-Fluorouracil plus Leucovorin versus 5-Fluorouracil alone for metastatic disease, this regimen is currently being employed. Even with locally recurrent lesions, the aggressive multimodality approaches including intra-operative irradiation have resulted in improved local control, and long-term survival rates of 20% to 25% versus an expected 5% with conventional techniques in historical series.
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PMID:The role of intra-operative irradiation in locally advanced primary and recurrent rectal adenocarcinoma. 158 87

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.
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PMID:Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. 161 79

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus II, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = less than .1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus II, 100% versus 60% at 3 years, p = less than .01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (3.3%) developed significant late treatment-related complications requiring hospitalization for management.
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PMID:Long-term results of infusional 5-FU, mitomycin-C and radiation as primary management of esophageal carcinoma. 170 62

In the last two decades, we have witnessed revolutionary advances in pancreatic imaging as well as increased availability of megavoltage radiotherapy equipment and sophisticated radiotherapy planning devices. Several advances in the radiotherapy of pancreatic cancer have been made for the patient with resectable disease. Postoperative radiotherapy combined with chemotherapy confers a survival advantage after 'curative' resection. Preoperative and intraoperative intraoperative radiotherapy may do the same, but this requires further evaluation. Preoperative irradiation may improve the resectability rate, but the clinical data are still very limited. For locally unresectable disease, PHD radiotherapy with adjuvant 5-FU should now be the standard treatment in suitable cases with a median survival time of about one year. High LET radiation beams have failed to produce improved survival in two prospective randomized studies. Intraoperative radiotherapy is an effective means of pain control and enhances control of local disease, but has not been shown to improve survival rate significantly. Interstitial radiotherapy also improves local control, but it is associated with a high mortality rate and an even higher major complication rate. Wide-area radiation therapy and preoperative radiotherapy both seem to show promise in this group of patients. Patients with metastatic disease should be treated palliatively on an individual basis.
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PMID:Radiotherapy in the treatment of pancreatic cancer. 170 32

Drug therapy is most often used in colorectal cancer for palliation of metastatic disease. Current data also support the use of adjuvant chemotherapy following complete surgical resection in patients with locoregional lymph node metastases. The agent most widely used in the treatment of colorectal cancer is the antimetabolite fluorouracil (5-fluorouracil; 5-FU). This fluoridated pyrimidine has been available for over 30 years, yet to date no other single agent has proven to be more efficacious. Controversy exists about the most desirable schedule for administration of fluorouracil. Efforts have been made to improve upon its therapeutic index and efficacy by using the concept of biomodulation, in which chemicals which are not themselves active antineoplastic agents against colorectal cancer are administered with fluorouracil in an attempt to enhance the sensitivity of the cancer cell to fluorouracil. Biomodulation agents currently in use in clinical practice include leucovorin (calcium folinate), methotrexate, and interferon-alpha. Other biomodulation strategies are currently under investigation. Adding putatively active antineoplastic agents to fluorouracil to form combination chemotherapy regimens has not yielded convincingly superior results to treatment with fluorouracil alone, and the toxicities of many of these combination regimens have been formidable. Secondary therapies following failure of fluorouracil-based regimens have been similarly disappointing. Current areas of investigation into the chemotherapy of colorectal cancer include development of new agents, locoregional administration of chemotherapy, and manipulation of intrinsic drug resistance mechanisms of the cancer cells.
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PMID:Drug treatment of colorectal cancer. Current status. 172 64

Chemotherapy is not a common treatment for cerebral metastases. The authors report results of combination chemotherapy with cisplatin (CDDP) and fluorouracil (5-FU). Sixteen men (age range 31-73 years) with brain metastases were treated with CDDP 20 mg/m2/day in continuous infusion for 5 days (d 1-5) and 5-FU 1 g/m2/day in continuous infusion for 4 days (d 1-4), and the treatment schedule repeated every 3 weeks. A brain computerized tomography after 2, 4 and 6 cycles was performed to assess efficacy. It was considered that complete response was achieved if no lesion was found on the CT scan, and partial response if at least half of the total volume had decreased. After 2 cycles, the response rate was therefore 8/16 (50%). Treatment toxicity was very mild with only 1 case of severe but reversible myelotoxicity (grade III). It is concluded that chemotherapy combination with CDDP and 5-FU is a useful treatment for brain metastasis of lung carcinoma.
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PMID:[Chemotherapy with cisplatin and 5-fluorouracil in inoperable brain metastases of bronchopulmonary cancers]. 175 34

To assess the feasibility and effectiveness of combined therapy on locally advanced cervical cancer, we entered 38 patients into a study. The patients were treated with mitomycin-C (10 mg/m2) on Days 1 and 30 and 5-FU (1000 mg/m2) on Days 1 to 4 and Days 30 to 33. In 5 weeks 4500-5000 cGy was given concurrently, followed by radioactive implants. Twenty-six patients had an early-stage disease (IB-IIB) and twelve had a late-stage disease (IIIB-IVA). Eighty-seven percent (33/38) of the patients had a tumor measuring 5 cm or more. The other 5 patients with a tumor size under 5 cm had biopsy-proven positive pelvic nodes; 2 of these 5 patients had a pretherapy hysterectomy. Tumor response, complete (CR) vs partial (PR), was assessed in 36 patients 3 months after completion of therapy. A CR was noted in 80% (29/36) of the patients. The PR status conferred a detrimental effect on the pelvic disease control (PDC), disease-free survival (DFS), and survival (S) while late stage correlated with the development of distant metastases (DM) and a poor DFS. PDC was obtained in 93% (27/29) of the patients who had a CR, as compared to only 43% (3/7) of those with a PR (P = 0.0228). The DFS and S rates were 59 and 77% for patients with a CR and 21 and 19% for those with a PR; respective P values were 0.0340 and 0.0002. Eleven percent (3/26) of the patients with an early stage developed DM, as compared to 50% (6/12) of those with late stage, (P = 0.0016). The DFS rates were 80 and 37% for patients with an early and late stage, respectively (P = 0.0141). Four patients developed transient neutropenia and one had transient thrombocytopenia. The second dose of mitomycin-C was omitted in 4 patients due to persistent neutropenia in 3 and to transfusion-related hepatitis in 1. Two percent (5/21) of the patients who had a staging laparotomy developed wound dehiscence. Three patients developed non-cancer-related small bowel obstruction requiring surgery. We concluded that this combined regimen was well tolerated. Although it was effective in controlling the cancer in the pelvis, this regimen failed to control DM in late-stage patients.
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PMID:Mitomycin-C/5-FU and radiation therapy for locally advanced uterine cervical cancer. 175 91

An advanced breast cancer patient refractory to CAF (Cyclophosphamide, Adriamycin, 5-fluorouracil), 5-FU-Methotrexate sequential therapy and Tamoxifen was treated with the combination 5' DFUR, MMC, Etoposide and MPA. Complete response was obtained both against liver and lymph node metastases from 7 months after the initial treatment. A mild bone marrow suppression and appetite loss were observed as the side effect. It is suggested that the combination therapy may be useful for previously treated patients with advanced breast cancer.
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PMID:[5'-deoxy-5-fluorouridine (5'-DFUR), mitomycin C (MMC), etoposide and medroxy progesterone acetate (MPA) in a previously treated patient with advanced breast cancer]. 182 14

The Radiation Therapy Oncology Group (RTOG) conducted a Phase I/II study in hepatocellular cancer that closed on September 9, 1987 and some results presented previously. Here, 17 patient characteristics are evaluated to identify any of prognostic significance. Two hundred sixteen patients were entered and 198 (74% with metastases and/or previous chemotherapy) were evaluable. Treatment began with an induction regimen of external beam radiotherapy to the liver (21.0 Gy, 3.0 Gy/Fx, 10 MV photons, 4 days per week) with low-dose chemotherapy (5-Fluorouracil (FU), 500 mg, i.v.; Doxorubicin, 15 mg, i.v.) on treatment Days 1, 3, 5 and 7. In the later stages of these studies, 56 patients received external beam radiotherapy as hyperfractionated treatment (1.2 Gy twice daily, 4 hours separation, 5 days per week, 24.0 Gy total) with similar chemotherapy. One month following induction therapy, cycles of radiolabeled antibody therapy were given every 2 months. Each cycle was derived from a different species of animal and consisted of 30 mCi I-131 antiferritin, Day 0, and 20 mCi, Day 5. On Day -1, 5-FU, 500 mg, and Adriamycin, 15 mg, were administered. The overall median survival for the entire group, including previously treated patients, was 4.9 months. The median survival for alpha-fetoprotein (AFP) - patients not previously treated was 10.5 months. Median survival for all AFP - patients was 8.5 months and for all AFP + patients was 4.6 months (p = 0.006). Of the 17 pretreatment characteristics investigated for prognostic value Karnofsky Performance Score (KPS) (80-100 vs. less than 80) (p = 0.0001), presence/absence of ascites (p = 0.0002), bilirubin level (less than 1.5 vs. greater than or equal to 1.5) (p = 0.018), SGOT (less than or equal to 35 vs. greater than 35) (p = 0.001); alkaline phosphatase (less than or equal to 95 vs. greater than 95) (p = 0.008) were found to be significant independently using a multivariant regression model. The relative risk of dying for the unfavorable component of each of these characteristics was 2.2, 2.0, 1.5, 1.9 and 1.7, respectively. Good and poor prognostic groups were then defined and compared to a similar patient population (RTOG study 83-19) with confirmation of the validity of the model. When stratification for these overpowering clinical factors was incorporated, AFP status was again significant with a relative death rate 1.80 times higher for AFP+ patients. Our recommendations for structuring future prospective randomized trials are discussed and include stratification by AFP status.
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PMID:Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01. 184 27

We retrospectively evaluated continuous intra-arterial infusion chemotherapy after hepatic resection for hepatic metastases of colorectal cancer. From 1982 to 1990, we treated 22 patients with continuous intra-arterial infusion chemotherapy after hepatic resection, and 43 patients with only hepatic resection. 5-FU (250 mg/day) was administered continuously through implantable reservoir immediately after hepatic resection, and continued as long as possible. The total dose of 5-FU administered was 1.75-46.0 g (mean 17.4 g). We divided the patients into three groups: the first was administered a total dose of 5-FU more than 15 g, the next with less than 15 g, and the last with only hepatic resection was not given 5-FU. The 5-FU group receiving more than 15 g showed the lowest rate of hepatic metastasis recurrence. We compared the group showing recurrence within six months after hepatic resection (early recurrent group) with the group evidencing recurrence on and after six months (late recurrent group). In the former group, extra-hepatic recurrence significantly increased, whereas in the latter group hepatic recurrence significantly increased (p less than 0.05). In the early recurrent group, moderately or poorly differentiated adenocarcinoma significantly increased (p less than 0.01). According to the pathological result of pre-operative biopsy, one should check for extra-hepatic lesion as much as possible, and choose systemic chemotherapy for the early recurrent group.
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PMID:[Evaluation of continuous intra-arterial infusion chemotherapy after hepatic resection of liver metastases in colorectal cancer]. 187 35


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