Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

Twenty patients with recurrent or persistent epithelial ovarian cancer failing conventional therapies were treated with a single intraperitoneal injection of iodine-131-labeled OC 125 monoclonal antibody. Rare acute side effects were nausea and mild diarrhea. At doses up to 120 mCi of iodine-131, median white blood cell and platelet count nadirs were 3.6k/microliters and 187k/microliters, respectively. Two patients acquired thyroid toxicities despite thyroid blockage with "cold" iodine. One patient had transient TSH elevation while remaining clinically euthyroid, and 1 patient developed activation of a thyroid nodule and clinical hyperthyroidism. Dose-limiting toxicity has not yet been observed. Twelve of 20 patients are alive 3 to 17 months following therapy. Tumor progression was noted in the majority of patients, although 3 patients had documented decreases in tumor burden of short duration. We conclude that, at the doses examined, iodine-131 OC 125 can be safely administered intraperitoneally.
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PMID:Intraperitoneal radiolabeled OC 125 in patients with advanced ovarian cancer. 276 26

We treated 19 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine, 52 per cent of whom had previously received and failed chemotherapy. Implantable pumps were used for automatic drug delivery. 5-Fluoro-2-deoxyuridine was infused continuously for 14 days at monthly intervals. The starting dose was 0.15 mg. per kg. per day (intravenous) or 0.25 mg. per kg. per day (intra-arterial). Intravenous doses were increased or decreased in increments of 0.025 mg. per kg. per day as permitted by toxicity. Abdominal pain, diarrhea and mucositis limited the intravenous infusion, while malaise, anorexia and hepatic function abnormalities limited intra-arterial infusion. Of 18 evaluable patients we observed 1 complete, 4 partial (objective response rate 28 per cent) and 2 minor responses. The duration of response ranged from 2 to greater than 18 months. During a median follow up of 7.5 months (range 2 to 21 months) only 4 of the 18 patients had objective tumor progression. Over-all survival for the 19 patients was 94 per cent. Continuous infusion of 5-fluoro-2-deoxyuridine may be effective for the treatment of progressive renal cell carcinoma.
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PMID:Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion. 296 42

In Columbus, OH, 46 patients with measurable metastatic colorectal cancer were treated with leucovorin (LV) 80 mg/m2/20 h intravenous (IV) infusion followed by 5-fluorouracil (5-FU) 400 mg/m2 IV bolus daily for three days and then once weekly. Many patients had liver (62%) and/or multisite metastases (53%), carcinoembryonic antigen (CEA) greater than 10 (76%), documented tumor progression before entry (51%), and tumor-related symptoms (36%), but also good performance status (84%). Prior therapy consisted of radiotherapy (RT) in 18%, chemotherapy in 22%, both in 4%, and none in 56%. There were 36% objective responses and 31% stabilization, which we believe is a significant change in the natural history of these patients. Median survival was 8 months. Improved survival was seen in patients with single- rather than multiple-site involvement. Decreasing CEA levels were seen in 59% (always in responders or patients with stable disease), and correlated with longer survival time (11.0 v 5.5 months, P = 0.01). Palliation of tumor related symptoms occurred in 75%, with or without antitumor effect. One patient with prior RT died of neutropenic sepsis after only the three-day load, so we now recommend only weekly therapy in previously radiated patients. Otherwise, toxicity was mild, manifest as weakness in 62%, nausea in 53%, or diarrhea in 47%, which was the most common dose-limiting side effect. The occurrence or absence of toxicity did not predict outcome. Because of equivalent efficacy, mild toxicity, and less expense, this regimen should be considered for patients who desire therapy.
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PMID:Leucovorin plus 5-fluorouracil: an effective treatment for metastatic colon cancer. 349 15

In order to redefine the effectiveness of 5-fluorouracil (5-FU) as palliative therapy in patients with metastatic colorectal carcinoma, and to compare the effectiveness of 6-thioguanine (6-TG) with that of 5-FU, we studied 176 patients with metastatic colorectal carcinoma in a randomized prospective trial (SEG 79G1268 ). The pretreatment performance status of all patients was greater than 50% (ambulatory), and there was an equal distribution of patients with favorable pretreatment characteristics into each of the treatment regimens. Complete responses were only seen to 5-FU, but were obtained in only 3% of instances. The overall complete plus partial response rates were not different for 5-FU (8%) versus 6-TG (3%), or for patients who had shown prior progression on chemotherapy and who then received 6-TG in a nonrandomized fashion (7%). The time to tumor progression on each of the treatment programs was similar, 1.0 months. Survival was also similar in each regimen in the randomized study (6.3 months for 5-FU versus 7.9 months for 6-TG). However, survival was only 4.8 months for patients with previously drug-resistant tumors treated with 6-TG in the nonrandomized arm. In 16 patients failing 6-TG who then received 5-FU, there were no objective responses. Similarly, in patients failing 5-FU on this study who then received 6-TG, there were no responses in nine patients. Dose-limiting toxicity was observed in 40% to 51% of patients, and consisted of myelosuppression, vomiting, or diarrhea. It is concluded that 5-FU is a minimally effective agent in a very small number of patients with metastatic colorectal carcinoma. The drug 6-TG is equally ineffective in this setting. Alternative treatment programs to the systemic use of 5-FU should be considered in patients requiring palliative chemotherapy.
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PMID:Prospective randomized reappraisal of 5-fluorouracil in metastatic colorectal carcinoma. A comparative trial with 6-thioguanine. 637 81

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever. Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-gamma. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-gamma. Because this phenomenon has also been observed in other patients, we advise caution when using interferon-gamma in patients with Kaposi's sarcoma.
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PMID:Treatment of atypical leishmaniasis with interferon gamma resulting in progression of Kaposi's sarcoma in an AIDS patient. 771 12

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.
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PMID:[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]. 864 22

Despite improvements in neurosurgical and neuroradiotherapeutic techniques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensification of effective chemotherapeutic agents followed by autologous bone marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administered to 11 children with malignant brain tumors: 10 had recurrent (n = 8) or progressive (n = 2) disease, and 1 was treated before progression. The histological diagnoses were medulloblastoma (3), glioblastoma multiforme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocytoma (1), and anaplastic oligodendroglioma (1). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative regimen included BCNU 600 mg/m2 and VP16 1500 mg/m2 in 5 cases, and thiotepa 900 mg/m2 and VP16 1500 mg/m2 in 6 cases. The median times to achieve a neutrophil count over 0.5 x 10(9)/l and a platelet count over 50 x 10(9)/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III-IV) was 18% and consisted of oropharyngeal mucositis and diarrhea. Among the 6 patients with measurable disease at the time of BMT there were 2 with stable disease, whereas 4 patients had tumor progression: all these patients died of tumor recurrence 2-10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a median follow-up of 20 months (range 3-67). These preliminary results show that high-dose chemotherapy and BMT may be effective in children with malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable. The most important variable prognostic for progression-free survival is the disease status at the time of transplantation.
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PMID:Etoposide-containing regimens with autologous bone marrow transplantation in children with malignant brain tumors. 945 71

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.
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PMID:Calcitonin-secreting tumors of the pancreas: about six cases. 959 18

Irinotecan hydrochloride (CPT-11) is reportedly effective for the treatment of refractory or recurrent ovarian cancer. We investigated the antitumor efficacy and toxicity of combination therapy with CPT-11 and cisplatin in 25 patients (mean age 55 years, range 35-73 years) with refractory or recurrent ovarian cancer who had previously undergone platinum-based combination chemotherapy. Patients received two or more courses of treatment consisting of 50 or 60 mg/m2 of CPT-11 on days 1, 8 and 15 and 50 or 60 mg/m2 of cisplatin on day 1 administered intravenously. All patients were evaluable for the response and the toxicity profile. Complete responses were obtained in two (8.0%) patients and partial responses were obtained in eight (32.0%) patients, giving an overall response rate of 40% (10 of 25 patients) (95% CI 23.0-59.0%). The median duration of response was 5.5 months (range 2-27 months), the median time to tumor progression was 6 months (range 3-28 months) and the median overall survival was 12 months (range 3-39+ months). Grade 3 or 4 neutropenia, which was the most frequent and severe toxic effect, occurred in 36 (54.5%) of the 66 treatment courses and in 16 (64.0%) of 25 patients. The nadir of the leukocyte count occurred on days 18-19. Neutropenia was reversed by short-term administration of granulocyte colony-stimulating factor for 2-10 days. Less serious hematologic effects and non-hematologic effects, such as diarrhea, were also observed. This preliminary study showed that this regimen of CPT-11 and cisplatin was effective in patients with recurrent ovarian cancer.
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PMID:Irinotecan (CPT-11) combined with cisplatin in patients with refractory or recurrent ovarian cancer. 968 85


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