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 increase the complete remission (CR) rate achieved with two cycles of cisplatin, continuous infusion fluorouracil (5-FU) and oral leucovorin (PFL) we added two antifolate drugs, methotrexate (MTX) and the lipophilic piritrexim (PTX), to the combination (PFL-MP). Twenty-eight patients with previously untreated Stage IV squamous cell carcinoma of the head and neck received 2 cycles of cisplatin 100 mg/m2 on day 1 followed by a 5-day continuous infusion of 5-FU at 800 mg/m2/day and 100 mg of leucovorin administered orally every 4 hours. MTX was administered at 40 mg/m2 IV on day 15 and PTX at 75 mg orally twice daily on days 22 to 26, with cycle 2 starting on day 36. After 2 of the first 5 patients had tumor progression between days 15 and 35, the regimen was intensified to MTX 50 mg/m2, PTX 100 mg twice daily and a cycle duration of 28 days. Local therapy consisted of surgery and/or radiotherapy with concomitant 5-FU and hydroxyurea (FHX) administered every other week. Eleven patients (39%, 95% confidence intervals 21-57%) had a CR, 9 (32%) had a PR, and four patients had no response. Four patients were unevaluable for response to PFL-MP. Patients with poor performance status or N3 disease were less likely to achieve a CR. Mucositis following PFL was the dose-limiting toxicity. Local therapy included surgery in 15 patients and FHX chemoradiotherapy in 19 patients. The administration of FHX in this setting proved feasible and the regimen was given near the intended dose intensity in the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: a feasible and active approach. 160 74

The present article studied the biological behaviour of T4a versus T4b tumors. Of 29 patients with T4a tumors, 24 were treated by radical cystectomy and 5 were treated by diversion alone on detecting pathologic gross adenopathies at laparotomy. Of these 10/28 (35.7%) are alive and tumor-free. Of 11 patients with T4b tumors, 7 were initially treated with systemic chemotherapy (6 M-VAC and 1 5-FU + ADM) which achieved a clinical response in 4; 1 (14.2%) was RCc. Posteriorly, all these patients underwent radical cystectomy that revealed 2 had RPp and 2 had tumor progression (N+), accounting for an RPp rate of 28.5% and tumor progression of 71.5%. Overall, with a mean follow-up of 13.3 months, only 1 patient is tumor free. The foregoing findings show the different behaviour of these two groups of patients with an incidence of tumor positive adenopathies of 48.2% and 72.7% and tumor-free survival of 35.7% and 9.0% for patients with T4a and T4b, respectively.
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PMID:[Stage T4 bladder cancer. Impact of neoadjuvant chemotherapy on T4b tumors]. 209 80

The Northern California Oncology Group (NCOG) conducted a nonrandomized phase II study to evaluate the benefit of a seven-drug chemotherapy protocol (NCOG 6G91) in patients with glioblastoma multiforme (GM). Time to tumor progression was the primary end point of the study. The treatment consisted of 5-FU and lomustine administered after surgery and before radiation therapy, hydroxyurea and misonidazole during radiation therapy, and procarbazine and vincristine alternated with carmustine and 5-FU after radiation therapy. Ninety patients entered the study; data from the 64 patients with GM who completed radiation therapy and at least started the postradiation chemotherapy regimen and returned for follow-up examination are analyzed in this report. The median time to tumor progression in the 64 adequately treated patients was 42 weeks; the 25th percentile value was 60 weeks. A Cox multivariate analysis showed that age and extent of surgical resection were important prognostic variables in patients with GM. The results of this treatment regimen were similar to those of a previous NCOG protocol (6G61), which consisted of hydroxyurea during radiation therapy followed by chemotherapy with carmustine or a combination of lomustine, procarbazine, and vincristine.
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PMID:Northern California Oncology Group protocol 6G91: response to treatment with radiation therapy and seven-drug chemotherapy in patients with glioblastoma multiforme. 301 2

Treatment results (CR/PR** 30-40%) with the combination of 5-FU and FA--a biomodulator of 5-FU action--indicate that FA/5-FU is superior to 5-FU alone in the treatment of advanced colorectal cancer. However the "optimal" dose and time schedule has not been properly defined either for FA or for 5-FU. Moreover, in spite of the promising reports with FA/5-FU, the benefit of chemotherapy in colorectal carcinomas remains unproven. One way to better define the impact on survival and palliation might be to select patients with a documented tumor progression prior to chemotherapy. In 2 prospective phase II studies with FA/5-FU, tumor progression was the essential eligibility criterion. In both studies an overall tumor control (CR/PR/MR/NC)** of progressive disease with relief of tumor-related symptoms in most of the patients was achieved. The median survival times exceeded 12 months. In progressive colorectal cancer these treatment results can be regarded as a significant change in the natural history of the disease. Moreover, such a procedure will help to define more homogeneous patient groups and contribute to a better comparability of different studies. Additionally, overtreatment of patients with slowly proliferating tumors can be avoided, particularly with respect to the subjective and objective side-effects of FA/5-FU combinations.
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PMID:Folinic acid (FA) plus 5-fluorouracil (FU) in progressive advanced colorectal cancer. 306 21

The purposes of this administration were to inactivate cancer cells liberated from the primary tumor, to prevent them from metastasizing to other organs and to treat established metastatic cancer. Sixty-one patients with advanced gastric cancer who had received preoperative 5-FU dry syrup administration and who had also undergone curative resection between 1976 and 1982, in addition to postoperative chemotherapy (more than 20 mg MMC, 5,000 mg 5-FU), (Group A) were admitted to the present study. Their survival rate was compared with that of 67 patients given curative resection for advanced cancer without preoperative 5-FU dry syrup, who received the same postoperative chemotherapy only (Group B) during the same period. The 5-year survival rate for Group A was 0.55 +/- 0.06, higher than the rate of 0.42 +/- 0.06 for Group B. Comparing the 5-year survival rates of both groups in terms of clinicopathological factors such as stage of cancer progression, serosal invasion, lymph node metastasis, and lymphangitic and blood vessel invasion, the 5-year survival rates for Group A were higher than those for Group B. There were significant differences for histological stage III and blood vessel invasion between the two groups. From these results, it is suggested that preoperative oral 5-FU dry syrup might be effective as an adjuvant therapy to surgery for gastric cancer.
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PMID:[End result of preoperative adjuvant chemotherapy with oral 5-FU dry syrup in gastric cancer]. 338 42

A prospective phase II evaluation of regional FUDR chemotherapy using a totally implantable drug infusion pump was conducted in 81 patients with colorectal metastases to the liver. The survival results were compared to a historical control group of 129 patients with isolated liver metastases. The two groups were comparable with respect to their dominant prognostic factors. The pump patients received their continuous chemotherapy on an outpatient basis and had an 88% response rate, as evidenced by a fall in their serum CEA levels by one-third or greater after two cycles of chemotherapy. By four criteria, the regional chemotherapy patients had an improved survival rate compared to the control series. First, the 1 year survival and median survival was better for the entire group of pump patients vs. controls (82% vs. 36%, 26 months vs. 8 months, p less than 0.0001). The survival for the regional chemotherapy patients was not influenced by the extent of tumor involvement, whether previous systemic 5-FU was given, or whether the patient had symptomatic disease. Second, the entire group of regional chemotherapy patients (including nonresponders) had a greater 1 year survival compared to the most favorable subgroup of control patients with the following characteristics: normal liver function tests, no symptoms, and only one lobe involved (82% vs. 66%, p = 0.009). Third, a subgroup of 49 pump patients, whose initial treatment for metastatic disease was regional chemotherapy (within 3 months of diagnosis) had a better 1 year survival than an exactly matched group of 49 control patients (67% vs. 30%, p = 0.000003). Fourth, the actuarial survival for all 81 pump patients was significantly better than predicted by a mathematical model constructed to predict the patient's clinical course based upon the seven dominant prognostic variables identified in a multifactorial analysis (82% survival at 1 year vs. 33% predicted survival). While liver metastases could be controlled in most patients, the major cause of death was tumor progression in extrahepatic sites, particularly lung metastases and abdominal carcinomatosis. Although it appears that regional chemotherapy with an implantable pump appears to prolong life by 12 to 18 months more than matched historical controls, these results must be confirmed by a randomized (phase III) prospective clinical trial.
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PMID:A prospective phase II clinical trial of continuous FUDR regional chemotherapy for colorectal metastases to the liver using a totally implantable drug infusion pump. 622 95

Studies were made of the therapeutic response of six human colorectal tumor lines serially transplanted in immunosuppressed mice. The tumors with adenomatous structure showed greater sensitivity against different cytotoxic agents than the gelatinous ones. Among the drugs, 5-FU, BCNU and MeCCNU proved to be the most effective, producing not only temporary but long-term regressions. BCNU had its maximal effect at a single, oral administration. 5-FU sensitive and insensitive lines showed an equal uptake and incorporation of radiolabeled 5-FU. Both the take rate and the growth of nontreated and treated tumors in the same host revealed the influence of host-defence mechanisms on tumor progression.
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PMID:Chemotherapeutic sensitivity of human colorectal tumor xenografts. 745

Primitive neuroectodermal tumors (PNET) of the female genital tract are rare and more common in the ovary, but uncommon in the cervix uteri. A 26-year-old woman presented with suspect cervical smears. The conization specimen showed a small cell non-keratinised squamous cell carcinoma with involved margins. The patient underwent radical abdominal hysterectomy and pelvic lymphonodectomy. The microscopic examination showed a densely cellular tumor of small neuroendocrine cells with scanty cytoplasm and rosettes. Immunohistochemically, the cells were slightly positive for NSE and negative for S 100, GFAP, neurofilaments, squamous cell cytokeratin 1, vimentin, desmin and leukocyte common antigen. The diagnosis of PNET, stage pT1b1,N0, M0 was made. The patient underwent adjuvant pelvic radiation. Three years later, pulmonary metastases occured. Radiation therapy of the thorax and six courses of combination chemotherapy (5-FU and cis-platinium) could not prevent tumor progression. The patient died 4.2 years after diagnosis. The autopsy showed widespread lymphatic metastases and hepatic, pulmonal and skeletal metastases and a peritoneal carcinosis. The tumors are resistent to radio- and chemotherapy, and the prognosis is generally poor. Up to 15% foci of squamous or glandular differentiation occur in or adjacent to these tumors. So the authors favor the histogenesis from a pluripotent endocervical stem cell. The neuroendocrine component of mixed tumors improve the prognosis. Therefore, it is necessary to recognize this component.
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PMID:Primitive neuroectodermal tumor of the cervix uteri. A case report. 906 88

Colorectal cancer is one of the leading causes of cancer death. The mainstay of chemotherapy in colorectal cancer patients for the past 40 years has been fluorouracil (5-FU). Oxaliplatin (Eloxatin) is a novel platinum compound with promising activity in colorectal cancer. As a single agent, oxaliplatin has produced response rates of 12% to 24% in patients with previously untreated advanced colorectal cancer, and 10% to 11% in patients with relapsed or refractory advanced colorectal cancer. In phase II trials, oxaliplatin combined with 5-FU, with or without leucovorin, was associated with response rates of 60% and higher when used as front-line therapy, and when used in patients with relapsed or refractory advanced colorectal cancer, response rates ranged from 25% to 50%. In the front-line setting, two randomized trials of 5-FU and leucovorin, with or without oxaliplatin, demonstrated that the addition of oxaliplatin significantly increases response rate and time to tumor progression, but not survival, over 5-FU plus leucovorin alone. The reasons for this discrepancy are unclear, and several possibilities are being considered. Additional phase III trials are underway to clarify the contribution of oxaliplatin in the treatment of patients with locally advanced and metastatic colorectal cancer.
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PMID:Efficacy of oxaliplatin in the treatment of colorectal cancer. 1120 66

Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to fluorouracil (5-FU) within cancer cells. Data from two large phase III trials performed in patients receiving first-line chemotherapy for metastatic colorectal cancer showed that capecitabine yielded higher objective response rates and equivalent median time to tumor progression and overall survival rates as 5-FU/leucovorin. In these studies, capecitabine demonstrated lower rates of diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin, but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural extension of this work has been to evaluate substitution of capecitabine for 5-FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin). This is especially important due to concerns regarding toxicities observed with regimens that combine bolus 5-FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase II trials of capecitabine in combination with irinotecan or oxaliplatin in patients with advanced disease indicate that the combinations are well tolerated and produce response rates that are in the range of those that would be expected with infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III trials have been initiated in the advanced disease and adjuvant settings and should help determine the efficacy, toxicity, and tolerability of the capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.
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PMID:Current status of capecitabine in the treatment of colorectal cancer. 1252 Jun 35


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