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)

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.
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PMID:Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study. 191 29

Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in forty-three patients receiving cisplatin-based combination chemotherapy for ovarian cancer. All patients were treated with broad-spectrum antibiotics including gentamicin. Twelve of fifty-six episodes were associated with positive cultures; in six patients a single organism was isolated, and the other six patients had polymicrobial infection. The mean duration of antibiotic therapy was 6.5 days. One patient died of sepsis. Fifty-five episodes had a successful outcome. There was no antibiotic-related morbidity. Based on this review we recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia with fever. The regimen of gentamicin plus ticarcillin and clavulanic acid (ceftazidime for penicillin-allergic patients) is effective as initial therapy. Additional agents (i.e., vancomycin) may be necessary in culture-positive patients based on sensitivity testing of bacterial isolates. Gentamicin can be safely administered to patients receiving cisplatin-based chemotherapy without compromising ability to continue cisplatin therapy in subsequent treatment cycles.
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PMID:Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy. 198 9

1. Widespread visceral and intestinal wall metastases are present in women dying with ovarian cancer. Intestinal wall invasion is commonly found at autopsy and is associated with bowel obstruction. Liver parenchymal replacement by metastases in more extensive than that in the lung, where most metastases have a subpleural location. Multifocality characterizes metastases in both of these organs. 2. Neoplastic lymphatic invasion is common. Lymphatic and blood vascular invasion are associated with an increased incidence of metastases in lymph nodes, small bowel wall, pancreas, lungs, ureter, and liver. 3. The mean survival time from diagnosis to death is less than 2 years. Both increasing neoplastic histological grade and clinical stage at diagnosis are associated with decreased survival time. 4. The most common causes of death are carcinomatosis, infection, or a combination of these processes. Sepsis, pneumonia, or both of these account for most of the fatal infections. 5. Bowel and ureteral obstruction constitute the most common forms of tumor-induced morbidity. The former process tends to be multifocal, involving the small and large intestines, and it is found during the disease course as well as at autopsy. Ureteral involvement is usually associated with hydronephrosis and is bilateral in approximately one fourth of the cases.
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PMID:The pathology and biologic behavior of ovarian cancer. An autopsy review. 265 34

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.
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PMID:Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer. 318 48

Thirty-two patients with Stage III or IV epithelial ovarian cancer and residual tumor volumes in excess of 2 cm in diameter after initial debulking were treated with platinum and cyclophosphamide chemotherapy. Twenty-seven patients (84%) received at least six courses of chemotherapy. Six patients developed grade 3 or 4 hematologic toxicity and one patient died with granulocytopenia and sepsis. The actuarial survival of the total group of patients was 78% at 12 months, 27% at 24 months, and 11% at 36 month. Of patients with residual disease 2-4 cm in diameter, 82% were alive 12 months after diagnosis and 46% were alive at 24 months. In contrast, patients with greater than 4 cm residual disease had a 12-month survival of 73% and a 24-month survival of only 7%. The size of residual tumor after surgery remains a very important prognostic factor in patients treated with platinum-based combination chemotherapy. Reoperation with further tumor debulking should be considered in ovarian cancer patients referred for chemotherapy with large volume residual disease to maximize response to combination chemotherapy.
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PMID:Prognostic implications of large volume residual disease in patients with advanced stage epithelial ovarian cancer. 357 60

Thirty-six patients with stage III-IV ovarian cancer, bulky disease, were treated with adriamycin and cyclophosphamide administered in two different dosages. Three or four cycles of chemotherapy were administered before the first surgery to facilitate the surgical debulking. After surgery, 6 additional cycles of chemotherapy were administered, and a second look was performed. Clinical CR + PR was observed in 19/30 (63%) evaluable patients after the first part of chemotherapy, but pathologic CR + PR was confirmed in only 13 (43%) patients. After the second part of chemotherapy and the second surgery, 5/30 (17%) patients had pathologic CR and 3/30 (10%) showed residual disease. The two regimens demonstrated similar activity (67% vs 56% clinical CR + PR) but a very different toxicity. In fact, 50% of patients treated with higher doses showed severe leukopenia and 25% severe thrombocytopenia, and 2/13 died of sepsis. The significant activity of adriamycin plus cyclophosphamide in ovarian cancer was confirmed, and increasing the dosage of the two drugs did not increase their activity but only their toxicity.
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PMID:Chemotherapy and surgery in the treatment of ovarian cancer bulky disease. 370 93

This case report presents an unusual case of primary IUD-associated ovarian actinomycosis, which spread to the sigmoid causing intestinal obstruction. A 43-year-old gravida 3, para 2, had her 1st IUD from 1978-80 (Gyne-T) and her 2nd IUD from 1980 to October 1983 (Multiload). Right lower abdominal pain led to hospitalization in May 1983. A tender nodular mass was palpated in the left pelvic area. Laboratory results confirmed the presence of inflammation. Rapid improvement followed a course of laxatives and cephalosporin antibiotics, and the patient was discharged with the diagnosis of acute sigmoid diverticulitis. 2 months later, a double contrast examination of the large intestine was done and showed severe narrowing of the sigmoid colon over a distance of 12 cm and occasional sharp recesses. Colonoscopy showed a spastic stricture of the sigmoid with massive edema of the otherwise intact mucosa at 18 cm. Computer tomography of the abdomen showed a large, focally cystic infiltrative mass in the pelvis with congestion and displacement of both ureters as well as bilateral hydronephrosis, predominantly on the right side. The descending colon was congested. The patient was readmitted to hospital with the tentative diagnosis of ovarian cancer when her general condition deteriorated. She complained again of abdominal pain in the right lower quadrant and alternating diarrhea and constipation. Pyrexia and the hematological findings suggested sepsis. The pelvis contained a predominantly leftsided nodular mass and a brown fetid discharge was coming through the cervix. The IUD was removed and treatment with ampicillin and clindamycin was started with rapid improvement in the patient's condition. Obstruction with extreme distention of the colon required emergency laparotomy. An inflammatory mass was found in the pelvis consisting of a right-sided ovarian tumor, bilateral hydrosalpinges, and a tightly encased sigmoid colon. The dilated caecum had a large necrotic area in its wall which necessitated caecostomy and double-current sigmoidostomy after subtotal hysterectomy and bilateral salpingo-oophorectomy. The patient made a good recovery. As recently as the 1950s, primary pelvic actinomycosis was a rarity. In the last 4 years alone, 20% of all reported cases of actinomycosis involved the female genital tract. The percentage of cases found among IUD users has been continuously increasing and in the last 2 years all published cases were IUD users. The presence of actinomyces in vaginal smears always is indicative of the presence of a foreign body, most commonly and IUD.
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PMID:IUD-associated ovarian actinomycosis causing bowel obstruction. 374 Sep 65

A phase II study combining etoposide with carboplatin and ifosfamide as salvage therapy in advanced ovarian cancer was undertaken. Objective responses were achieved in 37.5% of 16 evaluable patients with a mean progression-free interval of 8.6 months. Stable disease was present in 25% of patients; in 37.5% of patients the disease progressed on salvage. Based on original response to front-line therapy, patients were classified as being platinum-sensitive (group I) or platinum-refractory (group II). Clinical response to salvage therapy was seen in 44.5% of group I patients, but in only 28.6% of group II patients. This difference was not statistically significant. When a more precise definition of platinum sensitivity was applied, clinical responses were seen in 54.5% of group I patients, but no responses were noted among group II patients (p < 0.05). Platinum sensitivity appeared to be an important factor in achieving a response with this regimen. This combination was well tolerated, myelotoxicity being the dose-limiting toxicity encountered. No life-threatening, nonhematologic toxicities were seen. One death occurred secondary to nadir sepsis. The combination of etoposide, carboplatin, and ifosfamide is an active salvage regimen in patients with advanced ovarian carcinoma; however, severe myelotoxicities and inability to produce long-term responses underscore the need for continued trials to find a more durable salvage regimen.
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PMID:Phase II trial of etoposide, carboplatin, and ifosfamide as salvage therapy in advanced ovarian carcinoma. 823 77

A dose-finding study was performed in 27 ovarian cancer patients to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin. The median age of the patients was 55 years (age range, 30 to 74 years), the median performance status was 0 (range, 0 to 2), and the sizes of tumors residual to first surgery were identified as > or = 1 cm (14 patients) or less than 1 cm (13 patients). All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered as a 3-hour infusion at five dose levels, starting at 150 mg/m2 and increasing in 25 mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. Mild emesis, general alopecia, and moderate myalgias occurred. Hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 30% of patients. Grade 3 and 4 neutropenia lasted less than 7 days; no patients required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte/granulocyte-macrophage colony-stimulating factor was needed. Twenty-one patients were evaluable for response. Overall response rate (complete response+partial response) was 81%, and responses were observed at all paclitaxel dose levels. The maximum tolerated dose was not achieved. In conclusion, with a fixed dose (300 mg/m2) of carboplatin, paclitaxel can be administered by 3-hour infusion at 250 mg/m2 with manageable toxicity and no supportive care is needed.
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PMID:Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. 855 81

Amifostine (WR-2721) was originally developed as a radioprotective agent. In animals, it protects normal tissues from the damaging effects of irradiation and, as shown in more recent studies, of several cytotoxic agents. Protection of tumours is generally reduced compared with that of normal tissues in animals, suggesting that amifostine may increase the therapeutic window of cytotoxic therapies. Clinical data concerning amifostine suggest that cytotoxic chemotherapy-induced haematological toxicity and cisplatin-induced neurotoxicity, nephrotoxicity and ototoxicity are decreased upon administration of amifostine prior to cytotoxic drugs. Similarly, amifostine reduces damage to normal tissues caused by radiotherapy. Available data show that this protection is achieved without adversely affecting tumour response or patient survival. In 1 large trial, the reduction in cyclophosphamide- and cisplatin-related toxicities manifested as a decrease in the incidence and severity of neutropenia-related fever and sepsis and in the number of patients with ovarian cancer who discontinue therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced nephro- and neurotoxicity were reduced. Increased doses of cytotoxic therapy have also been administered when amifostine was given prior to therapy, which may increase tumour response. The predominant adverse effect associated with amifostine are hypotension, nausea and vomiting, somnolence and sneezing. Thus, amifostine is likely to be a useful adjuvant to the treatment of patients with malignancy, particularly those receiving cyclophosphamide plus cisplatin. discontinued therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced.
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PMID:Amifostine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. 861 69


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