Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.
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PMID:Gynecologic Oncology Group experience with ifosfamide. 215 88

Even though cisplatin-based combination chemotherapy results in increased clinical and surgical complete remission rates and improved median survival compared with single-agent alkylating agent chemotherapy, the 5 year survival rates for stages III and IV ovarian cancer have only improved to 25-30%. New methods being evaluated to improve response rates, median survival, and 5 year survival rates include the use of high-dose carboplatin, dose intensity using platinum compounds, intraperitoneal chemotherapy, concomitant intravenous and intraperitoneal chemotherapy, and the recent discovery of new active agents against epithelial ovarian cancer--Taxol, and Ifosfamide plus mesna.
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PMID:Ovarian cancer. 226 8

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.
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PMID:Phase II experience with ifosfamide/mesna in gynecologic malignancies: preliminary report of Gynecologic Oncology Group studies. 253 47

20 patients with F.I.G.O. stages III ovarian cancer were entered into a randomised trial between January 1980 and March 1984. After a surgical resection as complete as possible, 10 of these patients received an intravenous chemotherapy with Adriamycin, Vincaleucoblastin Bleomycin, Fluorouracil and Ifosfamid monthly for 10 months. The other 10 patients received the same combined chemotherapy but by a double route: Intravenously and intraperitoneally. The results were judged at "second look surgery". 1 Of the 10 patients who were treated intravenously, 2 who had had a complete surgical resection had no recurrence. Of the remaining 8 patients who had had an incomplete resection, 4 still had residual lesions that could not be removed completely.
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PMID:[Polychemotherapy of ovarian cancer via combined intravenous and intraperitoneal routes. Technic and preliminary results]. 376 Apr 80

Ifosfamide is a cyclophosphamide analogue synthesized in the 1960s with antineoplastic activity demonstrated in early broad-ranging phase I studies conducted in Germany in the 1970s. Because of significant urothelial toxicity, phase II studies in ovarian cancer in this country were delayed until the urinary epithelial protector mesna became available in 1985. Since that time, two well-executed prospective trials have shown that this agent produces measurable responses in about 20% of women with ovarian epithelial cancer recurring after primary chemotherapy and in 12% of those with tumors refractory to first-line therapy with regimens including cisplatin. Toxicity includes moderate to severe hematologic toxicity, renal dysfunction which is usually reversible, and CNS abnormalities including lethargy, somnolence, and disorientation. The risk of toxicity may be increased in patients with compromised hepatic or renal function and in those with hydronephrosis or hypoalbuminemia.
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PMID:Ifosfamide and mesna in epithelial ovarian carcinoma. 824 63

No new publication appeared in the past year on early stage ovarian cancer. The current GOG study will help determine the relative benefits and toxicities of intraperitoneal P32 versus cyclophosphamide and cisplatin in this group of patients. Recent studies in advanced ovarian carcinoma suggest a modest additional benefit for multidrug regimens, but cisplatin and cyclophosphamide remains an acceptable first line treatment for stage III and IV disease. Additional information on the use of carboplatin in advanced disease has been published, and this agent is now accepted as part of standard first line treatment programs. Platinum-based chemotherapy continues to be the mainstay of treatment for recurrent disease. With the commercial availability of taxol, a new salvage treatment is now available. Taxol will be increasingly studied as a part of front-line therapy as well as its role in the salvage setting. Altretamine and ifosfamide appear to have activity even in some patients with platinum-resistant disease, but these drugs will not likely have a major impact on ovarian cancer treatment. The use of high-dose chemotherapy with autologous bone marrow or peripheral stem cell support offers an exciting and potentially beneficial approach for patients with poor prognosis disease. The use of intraperitoneal chemotherapy and biologic agents continues to be problematic, and additional improvements are needed before they are considered useful outside of a research setting. With the exception of P32 for early stage disease, radiation therapy is likely to continue to play a minor role in the treatment of ovarian cancer. Few studies involving non-epithelial ovarian carcinomas were published during the past year. A definitive report was published demonstrating the activity of cisplatin-based chemotherapy (BEP) in patients with advanced dysgerminoma. Chemotherapy which preserves fertility provides an effective alternative to irradiation. Cisplatin-based chemotherapy was active in mixed mullerian tumors of the ovary although the prognosis of these patients was worse than patients with epithelial ovarian cancer. Concurrent chemotherapy added to irradiation has not improved survival over radiotherapy alone in patients with cancer of the uterine cervix. Patients still failed locally and distantly. Extended field irradiation to involved paraaortic lymph nodes with weekly cisplatin generated promising pilot data. Randomized trials evaluating the use of neoadjuvant chemotherapy prior to pelvic radiotherapy showed no benefit and increased toxicity. Ifosfamide alone or in combination regimens is an active drug but with serious side effects which require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gynecologic malignancies. 831 18

Ifosfamide has been assessed in the treatment of ovarian cancer for more than two decades. The drug possesses well-documented but modest activity (10% to 15% range) in women with platinum/alkylating agent-resistant ovarian cancer. A potentially important ongoing clinical trial is attempting to define the level of activity of ifosfamide administered in the salvage setting to patients with advanced ovarian cancer who have been previously treated with a platinum drug plus paclitaxel but not an alkylating agent.
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PMID:Ifosfamide in the treatment of ovarian cancer. 867 49

The successful outcome of ovarian cancer therapy with alkylating agents and cisplatin is seriously hampered by the development of acquired drug resistance. An increase in intracellular glutathione (GSH) levels in cancer cells is one of the major mechanisms involved. Depletion of GSH overcomes drug resistance and restores the chemosensitivity of malignant cells. Ifosfamide (IFEX), an alkylating agent, has been demonstrated to decrease intracellular GSH levels in vitro in malignant cell lines and in vivo in peripheral blood lymphocytes (PBL) obtained from patients with cancer. We studied the effect of IFEX on intracellular GSH levels in PBL isolated from patients with advanced ovarian cancer who were receiving chemotherapy. A total of 14 patients received IFEX plus mesna as a continuous infusion (1 g/m2 per day) for 6 consecutive days and cisplatin (100 mg/m2) as a 24-h continuous infusion on the 6th day. PBL were isolated prior to the initiation of chemotherapy and on the 3rd and 6th days of IFEX infusion. Intracellular GSH levels were determined by a modification of Tietze's method. IFEX caused a 20% or greater suppression of intracellular GSH levels in nine patients, eight of whom achieved complete remission of their disease. Six patients responded poorly to this chemotherapeutic regimen, five of whom showed no significant suppression of GSH levels. These data suggest that IFEX suppresses intracellular GSH levels in PBL from patients with ovarian cancer and that this suppression correlates closely with the subsequent clinical outcome.
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PMID:Effect of ifosfamide on intracellular glutathione levels in peripheral blood lymphocytes and its correlation with therapeutic response in patients with advanced ovarian cancer. 911 72

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.
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PMID:Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study). 951 2


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