Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.
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PMID:Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. 277 81

Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% +/- 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +/- 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T less than pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3-4M0 patients who achieved CR versus 33% of 100 with N0-+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% greater than or equal to 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.
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PMID:Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. 281 54

To assess the efficacy and safety of Adriamycin (Adria Laboratories, Columbus, OH) in inoperable hepatocellular carcinoma (HCC), 60 patients were randomized to receive Adriamycin 60 to 75 mg/m2 at 3-week intervals and 46 patients to receive no antitumor therapy. The median survival rate of the Adriamycin group was 10.6 weeks; that of the group receiving no antitumor therapy was 7.5 weeks (P = 0.036). Adriamycin induced tumor regression of 25% to 50% in 5% of patients and of over 50% in only 3.3% of patients. It caused fatal complications (septicemia and cardiotoxicity) in 25% of patients. The severity of neutropenia leading to septicemia for a particular dose was unpredictable. Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin. We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC.
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PMID:Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. 283 80

The efficacy of two chemotherapy regimens for recurrent and inoperable squamous cell carcinoma of the head and neck is reported. All patients had failed prior surgery and/or radiotherapy. 23 patients (group A) were treated with Cisplatin 120 mg/m2 and Adriamycin 60 mg/m2. 21/23 were evaluable for tumour response. The overall response rate (RR) was 28.5% (6/21, 2 CR and 4 PR). Methotrexate 250 mg/m2 with Leucovorin-Rescue 5 X 10 mg/m2 and 5-Fluorouracil 600 mg/m2 were administered to 28 patients. In 26 evaluable patients a RR of 38.4% (10/26, 5 CR and 5 PR) was achieved. The responders in groups A and B had a median survival of 98 and 85.5 weeks respectively and the non-responders 27 weeks in both groups. Nausea, vomiting and alopecia were common and severe in the DDP/ADM group. The major toxic effect of MTX/5-FU was neutropenia with two associated deaths from septicemia, although subjective side-effects were almost completely absent. MTX/5-FU can be recommended for the palliative treatment of recurrent squamous head and neck cancer because of an acceptable response rate, good subjective tolerance and the possibility of outpatient treatment.
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PMID:[Chemotherapy of recurrent squamous cell carcinomas in the ENT area with cisplatin/adriamycin (DDP/ADM) and methotrexate/5-fluorouracil (MTX/5-Flu): a retrospective comparison of 2 protocols]. 374 8

Between January 1975 and December 1983 in the Cancer Institute, Montpellier, France, regional surgery (RS) was performed on 18 Stage III and 3 Stage IV patients (International Federation of Gynecology and Obstetrics [FIGO]) with histologically proven cystadenocarcinoma of the ovary. All patients were placed into one of three nonrandomized groups: Group A (9 patients), RS at first-look surgery; Group B (7 patients), RS at second-look surgery; and Group C (5 patients), RS at third-look surgery. Group A was given adjuvant chemotherapy, whereas Group B and C patients underwent nonregional surgery at first- or second-look operation, and received chemotherapy supplemented in some Group C cases by radiotherapy before RS. The adjuvant chemotherapy consisted of: cyclophosphamide plus Alkeran (mephalan) plus 5-fluorouracil (the first 7 patients) and Adriamycin (doxorubicin) plus cisplatin plus hexamethylmelamine (14 additional patients). RS consisted of basic procedures--abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy--and specific procedures--abdominal and pelvic peritonectomy; either total or partial colectomy; jejunoilectomy, leaving at least 150 cm of the jejunum; and retroperitoneal lymph node dissection aimed at maximal cytoreduction of tumor mass. There was no operative mortality. The overall postoperative morbidity was 33.3% (seven patients) due to wound sepsis. The survival from the beginning of treatment (absolute survival [AS]) and survival after RS (RSS) were compared. In Group A (AS = RSS) the probability of survival at 112 months (6/9 patients are still alive) was 0.52. In Groups B and C the median survival times (AS and RSS) were 37 and 17 months and 18 and 1 month, respectively. The difference in AS among the three groups of patients was not statistically significant (log-rank test), whereas the RSS was statistically significant between Group A versus Groups B, C, and Groups B and C combined (P less than 0.05).
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PMID:Aggressive regional surgery for advanced ovarian carcinoma. 394 Jun 14

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.
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PMID:Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma. 403 26

Seventy-eight patients with disseminated testicular cancer were entered on a random prospective study evaluating three separate remission induction arms. Therapy with cis-diamminedichloroplatinum (20 mg/M2 for five consecutive days every three weeks for 3-4 courses) and bleomycin (30 units intravenous push weekly for 12 consecutive weeks) was constant. Patients were allocated at random to one of the following induction regimens (in combination with platinum plus bleomycin): (1) vinblastine 0.4 mg/kg every three weeks for four courses; (2) vinblastine 0.3 mg/kg every three weeks for four courses; or (3) vinblastine 0.2 mg/kg plus Adriamycin 50 mg/M2 every three weeks for four courses. All patients received maintenance therapy with vinblastine 0.3 mg/kg once a month for 20 months (total therapy two years) unless progressive disease intervened. The incidence of granulocytopenic fever and sepsis was highest with regimen 1, as 9 patients (35%) developed granulocytopenic fever requiring hospitalization and antibiotics; only 4 (15%) patients on regimen 2 developed granulocytopenic fever. No patients on regimen 2 had documented sepsis. Fifty-three patients (68%) achieved complete remission and an additional 11 patients were rendered free of disease with surgical resection of residual localized disease. Fifty-three patients (68%) remain alive and continuously free of disease from 15+ to 39+ months. There was no difference in the complete remission rate or disease-free status with the higher dosage of vinblastine (regimen 1) during remission induction therapy compared to the less toxic lower dosage of vinblastine (regimen 2). This suggests that dosage reduction of vinblastine to 0.3 mg/kg can produce equivalent therapeutic results with diminished toxicity, and we no longer recommend the 0.4 mg/kg vinblastine dosage.
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PMID:Chemotherapy of disseminated testicular cancer. A random prospective study. 615 70

The development of drug resistance limits the survival or patients with small cell anaplastic carcinoma of the lung (SCLC). The present study was undertaken to overcome this problem by administering two alternating noncross resistant combination chemotherapy regimens. One-hundred-one patients were entered on study, and 98 were evaluable, with a median onstudy time of 55+ weeks. All patients received the initial combination therapy of cyclophosphamide, methotrexate, and vincristine, alternating every three weeks with Adriamycin and VP16-213 (etoposide). Radiation therapy was not a standard part of protocol. Thirty-two patients had regional disease (LD), and 66 had extensive disease (ED). Overall, 76% of patients responded to this therapy with 30 (31%) complete remission (CR) and 44 (45%) partial remissions (PR); the respective CR and PR rates were 31% and 50% for LD, and 30% and 42% for ED patients. Myelosuppression was the principal toxicity with a leukocyte nadir of 2.0 X 10(9)/1 in 10% of cycles. Septicemia in six neutropenic ED patients with progressive disease contributed to the only treatment-related deaths. Patients entering CR had a median survival greater than 51 weeks (range, 8-150+); 58+ for LD and 49+ for ED patients. Patients in PR had respective median survivals of 33+ (overall), 43+ (LD), and 24+ (ED) weeks. Forty patients have had relapses with initial sites being local sites in 35%, and neurologic in 38%. Although this protocol has not discernibly delayed the onset of drug resistance, the problem should be considered when new protocols are designed in SCLC.
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PMID:Alternating non-cross-resistant combination chemotherapy for small cell anaplastic carcinoma of the lung. 628 Aug 40

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as peripheral necrosis of the tumor, which was thought to be the result of the cytotoxic effect of DTIC. From this experience and because of the grim prognosis in patients with recurring parathyroid carcinoma, it may be that aggressive use of chemotherapy with DTIC early in the course of treatment should be considered.
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PMID:Parathyroid carcinoma: biochemical and pathologic response to DTIC. 650 66


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