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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucositis induced by chemotherapy is a painful and often dose-limiting side effect of cancer therapy. Furthermore, loss of the integrity of the oral epithelium often provides a microbial portal of entry and leads to sepsis. The present study describes the first animal model for chemotherapy-induced mucositis. The combination of three intraperitoneal injections of 5-fluorouracil at 5-day intervals and superficial mechanical mucosal irritation resulted in clinical breakdown of the oral mucosa characterized by ulcerative mucositis in Golden Syrian hamsters. Both clinical and histologic evaluation demonstrated that these changes were similar to those described in human beings and followed a pattern influenced by the degree of myelosuppression. This model should be of significance in establishing the stomatotoxicity of new chemotherapeutic agents, in evaluating medicaments to treat mucositis, and in studying the influence of oral mucosal breakdown on sepsis in myelosuppressed persons.
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PMID:An animal model for mucositis induced by cancer chemotherapy. 232 35

Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno-occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower.
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PMID:[Treatment of resistant or relapsing Hodgkin's disease with high doses of chemotherapy followed by autologous bone marrow transplant]. 232 65

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma. 211 72

Thirty-six of 39 previously untreated evaluable patients with advanced metastatic seminoma (stage greater than or equal to IIb) obtained a complete response (CR) and three a partial response (PR) after cisplatin-based combination chemotherapy with or without surgery/radiotherapy (group 1). After a median observation time of 36 months, 33 patients are alive with no evidence of disease (NED). Fifteen additional patients received cisplatin-based chemotherapy due to relapsing seminoma after initial radiotherapy (group 2). Thirteen patients obtained a CR, and two a PR. Patients from group 1 lived significantly longer after the start of chemotherapy than those from group 2. The rate and severity of the treatment-related complications were comparable in both groups. The most frequent nonfatal side effects of cisplatin-based combination chemotherapy were Raynaud-like phenomena, polyneuropathy, and myelosuppression. Four patients developed fatal complications (septicemia, bone marrow aplasia). In three of 12 patients with evaluable postchemotherapy histology, vital malignant seminoma was found. Cisplatin-based combination chemotherapy in advanced seminoma patients is highly effective, but includes a significant risk of severe complications. Less toxic treatment regimens should be explored, at least for patients who have less advanced tumors (stage IIb/limited stage IIc).
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PMID:The treatment of advanced metastatic seminoma: experience in 55 cases. 243 60

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.
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PMID:A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up. 245 78

205 patients with germ cell tumors were entered into the GPO Cooperative Study MAKEI 83/86 and classified as follows: 97 teratomas, 66 yolk sac tumors, 22 dysgerminomas, 17 embryonal carcinomas and three choriocarcinomas; 20% of all tumors were classified as mixed histology. Predominant primary sites were the ovaries (91 pts), the saccrococcygeal region (74 pts), the mediastinum (12 pts), the peritoneal cavity (10 pts) and other sites (18 pts). The treatment of teratomas was primarily surgery. Localised dysgerminomas received radiotherapy following surgery, in advanced stages (III, IV) four courses of chemotherapy vinblastine 3 mg/m2/day (days 1 + 2), bleomycin 15 mg/m2/day (days 1-3) and cisplatinum 20 mg/m2/day (days 4-8) (VBC) were applied. The other fully malignant tumors received four courses of VBC chemotherapy, in extragonadal primary tumors and advanced stages of all sites additional four courses of VP16 100 mg/m2/day (days 1-3), ifosfamide 1500 mg/m2/day (days 1-5) and cisplatin 20 mg/m2/day (days 1-5) (VPIC) were administered. To avoid mutilating surgery in advanced disease, four courses of VBC chemotherapy were administered prior to resection. The relapse-free survival according to Kaplan-Meier for protocol patients with teratomas is 0.97 +/- 0.01, for dysgerminomas 0.73 +/- 0.09 and for other fully malignant histologic entities 0.81 +/- 0.02 with a median period of observation of 31 months. The toxicity mainly consisted of myelosuppression during VPIC chemotherapy in 39 of 62 pts resulting in twelve incidents of sepsis with lethal outcome in two pts. Impaired renal function was reported in 14 pts, the incidence of neuropathy, ototoxicity and pulmonary toxicity was negligible. For the follow-up study a reduction in chemotherapy seems justified in patients with favourable prognosis. The substitution of VP16 for vinblastine may result in reduced toxicity.
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PMID:[Non-testicular germ cell tumors: analysis of the therapy study MAKEI 83/86 anc changes in the protocol for the follow-up study]. 247 83

In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.
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PMID:Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. 250 90

Twenty-two patients with metastatic colorectal carcinoma were treated in a Phase I-II study of combination therapy with 5-fluorouracil (5-FU) and etoposide (VP-16). Treatment consisted of weekly intravenous VP-16, 100-120 mg/M2, followed by 5-FU, 400-480 mg/M2, in 28-day cycles. Myelosuppression was the dose-limiting toxicity with a mean nadir leukocyte count of 3,600/mm3 and a mean nadir thrombocyte count of 101,000/mm3. There were no episodes of sepsis or bleeding. The tolerable dose for this regimen is VP-16, 110 mg/M2, and 5-FU, 440 mg/M2, weekly. A total of 63 cycles of chemotherapy were given. Although 10 patients had stabilization of disease, no partial or complete responses were documented. We conclude that there is no clinical support for the in vitro synergy observed with this combination. Further trials of this combination using this schedule in colorectal carcinoma are not indicated.
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PMID:A phase I/II trial of 5-fluorouracil and etoposide in metastatic colorectal carcinoma. 258 29

Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.
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PMID:Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract. 258 30

Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M-VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing.
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PMID:Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern. 259 80


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