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)

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty 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 h) 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. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
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PMID:Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy. 244 31

One hundred seventy-three patients were treated 256 times with chemotherapy supported by autologous bone marrow transplantation during the past 9 years. The two most commonly used protocols were (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg) and (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 100 mg/m2 + CDDP 100-150 mg/m2). Among 115 patients in the therapeutic setting in which two courses were usually given, 75 were evaluable and the overall response rate was 42.7% with 12.0% CR rate. Breast and pediatric groups responded well; the response rate in breast cancer was 67.9% with 21.4% CR rate. Two patients with breast cancer who had multiple distant metastases and 2 pediatric patients are now alive with NED after 5 years of the treatment and seem to have been cured. The results in adjuvant settings have also been quite promising, e.g., 79.4% 5-year survival probability among breast patients mainly in stage III. Although drops of blood cell counts to the nadirs (WBC counts: less than 100-300) could not be prevented, the periods of myelosuppression appeared to have been effectively shortened so that the patients could be safely managed with intensified general supportive measures. Platelet counts are usually less affected, but the recovery is slower than for WBC counts. There were 13 patients who died within 10 weeks of the initiation of the treatment. Two of them succumbed to sepsis, and progressive disease was the cause of death in 8 patients whose terminal phases were undoubtedly affected by some infectious problems. We have shown that there are inverse relationships between infused numbers of CFU-GM and marrow recovery judged by the duration of neutropenia and the time required for neutrophils to recover over 500. Our recent laboratory experiments testing CFU-E, BFU-E and CFU-Mk in addition to MNC counts and CFU-GM showed that vulnerabilities of marrow progenitors seem to differ from cell lineage to cell lineage. This must therefore be taken into careful consideration in pursuing marrow transplantation.
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PMID:[Autologous bone marrow transplantation as a measure against myelosuppression in cancer chemotherapy]. 265 12

The Radiation Therapy Oncology Group conducted a Phase III single blind trial to evaluate the addition of Levamisole to post-operative thoracic irradiation (200 cGy five times weekly to a total of 5000 cGy plus 1000 cGy boost) in patients with resected RTOG Stage II-III non-small cell lung cancer with positive nodes. Between February 1980 and February 1983, 74 patients from 18 RTOG institutions were randomized; accrual to this study was prematurely terminated due to poor accrual and the inferior survival observed in the levamisole-treated patients on another RTOG trial. Sixty-four patients were evaluable; 32 assigned to levamisole and 32 were assigned to placebo. Over 95% of the patients have been followed for a minimum of 4 years or to death. Two patients on placebo and 5 on levamisole experienced Grade 3 pneumonitis or esophagitis; 1 patient on placebo and 2 on levamisole experienced Grade 3 pulmonary fibrosis. Three patients on levamisole experienced other Grade 3 or 4 toxicity: 1 case of intractable nausea and vomiting and 2 with Grade 4 neutropenia (less than 500 per mm3). There were no fatal complications. Median disease-free survival was 13 months in the placebo group and 9 months for the levamisole group. Median time to distant metastases was 18 and 12 months, and median survival was 20 and 13 months, respectively. We concluded that this study failed to demonstrate an advantage for levamisole.
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PMID:Post-operative thoracic irradiation with or without levamisole in non-small cell lung cancer: results of a Radiation Therapy Oncology Group Study. 282 70

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.
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PMID:VP-16 and cisplatin as first-line therapy for small-cell lung cancer. 299 6

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
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PMID:Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. 311 35

Advanced gynecologic neoplasms continue to pose major therapeutic problems; 22,500 deaths were estimated for 1987. Between December 1983 and October 1985, there were 25 patients evaluated at our institution who on joint evaluation by the radiation oncologist and gynecologic oncologists were found to have extensive disease not amenable to standard therapy. Patients were to be treated by a combined modality approach with Mitomycin-C and 5-Fluorouracil given concomitantly with radiotherapy. Nineteen patients were treated definitively and six patients were treated with palliative intent (24 primary, 1 recurrent). The patients ranged in age from 27 to 90 years with a mean of 57.3 and a median of 57. Primary sites at presentation were: cervix--14 patients, vagina--7 patients, and vulva--4 patients. The initial FIGO stages at time of the initial diagnosis were: Stage I--1 (recurrent), Stage II--4, Stage III--15, and Stage IV--5. Chemotherapy consisted of 5-fluorouracil 1 gm/m2 given continuous infusion for 4 days with Mitomycin-C 10 mg/m2 IV push on day 1. Radiation therapy was started on day 1. Only 2 of 25 patients (8%) required chemotherapy reductions. All 25 patients received mega-voltage irradiation. The external beam dose range was 2000-6500 cGy and 14/25 patients received intracavitary or interstitial therapy. In the definitive patient group, there was no reduction in the therapeutic dose. Only four patients underwent surgical therapy. With a minimum follow-up of 8 months and a median follow-up of 28 months, the survival for the entire population was 56%. Fourteen of the 19 patients (74%) treated definitively are surviving with 12 patients having no evidence of disease. Survival by site in the definitive therapy group was cervix--70%, vulva--100%, and vagina--66%. The overall response rate was 84% at 3 and 9 months (3 months; CR--36%, PR--48%, and 9 months; CR--60%, PR--24%). There were no local recurrences in the 12 patients who achieved a complete response. Three patients died of metastatic disease alone and the overall local control was 60%. Evaluation of therapeutic side effects was performed. Hematologic analysis by the Southeastern Oncology Group criteria showed neutropenia in 14 patients (1--life-threatening, 2--severe, and 11 patients--mild/moderate) and thrombocytopenia was observed in 11 patients (all mild or moderate). All hematologic complications resolved. Acute complications did not appear increased except for the addition of mild oral mucositis (12 patients). Six patients demonstrated late effects with only 2 patients felt to have severe complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Concomitant 5-fluorouracil, mitomycin-C, and radiotherapy for advanced gynecologic malignancies. 314 19

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.
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PMID:Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma. 348 11

Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases. Diminished polymorphonuclear leukocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections. The usual signs and symptoms of infection may be absent or altered in a compromised host. Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data. Synergism has most often been demonstrated in combinations that utilize a beta-lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside. Triple drug therapy has not been shown to be advantageous. Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients. Patients with blood deficient in granulocytes (granulocytopenic) who respond to 2-drug therapy but remain deficient in neutrophils (neutropenic) may need continued treatment until the neutropenia subsides. Those who do not respond and remain febrile with an unclear focus of infection may need to be started on antifungal therapy in addition to the antibacterial agent. The use of oral agents for the prophylaxis of neutropenic patients against bacteremia remains controversial. If drugs are used, co-trimoxazole and nystatin suspension may be preferable.
Cancer Metastasis Rev 1987
PMID:Antibacterial therapy in patients with malignancies. 354 37

Twenty-four patients with recurrent or widespread adenocarcinoma of the cervix were treated with combination chemotherapy. The drugs used were 5-fluorouracil (5-FU) (500 to 800 mg/m2), doxorubicin (40 to 50 mg/m2), and cisplatin (50 to 60 mg/m2). The chemotherapy was administered as a 76-hour continuous infusion via a silastic central venous catheter and repeated every 28 days. The total response rate was 42% (25% complete and 17% partial). Median duration of response was 7 months. Areas of response were usually lung and lymph node metastases. Toxicity, mainly neutropenia, was acceptable. All patients relapsed. This combination chemotherapy results in a modest response rate for a malignancy about which there is little information regarding the treatment of disseminated disease. Future studies should determine the activity of this combination administered in a bolus fashion.
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PMID:Combination chemotherapy for metastatic or recurrent adenocarcinoma of the cervix. 365 59


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