Chemotherapy in Advanced Ovarian Carcinoma: Current Standards of Care Based on Randomized Trials

Thigpen, Tate; Vance, Ralph B.; Puneky, Louis V.; Khansur, Tawfiq

doi:10.1006/gyno.1994.1347

Cited by 58 publications

(33 citation statements)

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“…If such a doseresponse effect is clearly established, it would be logical to give higher doses of paclitaxel with the support of growth factors. In a recent review of treatment for ovarian cancer, it was recommended that the standard first-line chemotherapy for advanced ovarian carcinoma should be a combination of paclitaxel plus a platinum compound (Thigpen et al, 1994). Our study, albeit with only a small number of patients, suggests that paclitaxel plus carboplatin may have an advantage over the combination of paclitaxel and cisplatin in terms of toxicity profile.…”

Section: Paclitaxel Pharmacokineticsmentioning

confidence: 60%

A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer

Siddiqui

Boddy²,

Thomas³

et al. 1997

Br J Cancer

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Summary The aim of this phase study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-'min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated with paclitaxel followed by a 30-min infusion of carboplatin. Paclitaxel dose was escalated from 150 mg m-2 to 225 mg m-2 in cohorts of three patients. Carboplatin dose was based on renal function. Pharmacokinetic studies were performed in nine patients (at least two at each dose level). A total of 66 courses were evaluable for assessment. Grade 3 or 4 neutropenia was seen in 70% of the courses, however hospitalization was not required. Grade 3 or 4 thrombocytopenia occurred in 24% of the courses. Alopecia, myalgia and peripheral neuropathy were common but rarely severe. The pharmacokinetics of paclitaxel was non-linear and did not appear to be influenced by co-administration of carboplatin. The AUC of carboplatin was 7.0±1.4 mg ml-' min, indicating that there was no pharmacokinetic interaction. The combination of carboplatin and paclitaxel may be administered as first-line treatment for advanced ovarian cancer. Although myelosuppression is the dose-limiting toxicity of the component drugs, the severity of thrombocytopenia was less than anticipated. The results of this study, with only a small number of patients, need to be confirmed in future investigations.

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Section: Paclitaxel Pharmacokineticsmentioning

confidence: 60%

A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer

Siddiqui

Boddy²,

Thomas³

et al. 1997

Br J Cancer

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“…3,4 New drugs, especially paclitaxel, have improved the prognosis. [5][6][7] Highdose chemotherapy regimens also appear to increase time to relapse and overall survival due to a favorable doseresponse. 8,9 Some immunotherapy agents such as intraperitoneal interleukin-2 (IL-2) have also been used with some success.…”

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confidence: 99%

Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients

Bay

Fleury

Choufi

et al. 2002

Bone Marrow Transplant

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Summary:Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the real clinical efficacy of graft versus cancerous ovarian cells.

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“…1 Despite advances in surgery and chemotherapy, the clinical outcome of most patients with advanced ovarian cancer remains poor. 2,3 Thus, it is imperative to advance our knowledge regarding the tumorigenic mechanisms underlying this deadly cancer. Such advances may provide opportunities for identifying molecular targets for novel therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Analysis of EphA2 expression and mutant p53 in ovarian carcinoma

Merritt¹,

Thaker²,

Landen³

et al. 2006

Cancer Biology & Therapy

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The EphA2 tyrosine kinase receptor is frequently overexpressed in ovarian cancer and this feature is predictive of poor clinical outcome. Preclinical investigation has also linked EphA2 with p53. In our present study, we examined EphA2 and p53 status (both expression and full-length mutation status) in 6 ovarian cell lines and 79 human ovarian cancers to determine potential associations. EphA2 was overexpressed in 80% of ovarian cancer cell lines and in 75% of clinical specimens. In particular, high levels of EphA2 occurred in 91% of tumors with p53 null mutations compared to 68% in tumors with wild-type or missense mutations (p = 0.027). EphA2 expression did not relate to critical versus noncritical site missense p53 mutations or the location of mutations on specific p53 exons. We also demonstrated that while EphA2 and p53 can provide independent information regarding clinical status, the combination of EphA2 and p53 status can predict poor clinical outcome. In particular, the combination of EphA2 overexpression and p53 null status was associated with decreased overall patient survival and related to increased incidence of ascites and distant metastasis. Taken together, these data indicate a complex relationship between EphA2 and p53 that appears to regulate EphA2 expression and clinical outcome.

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Chemotherapy in Advanced Ovarian Carcinoma: Current Standards of Care Based on Randomized Trials

Cited by 58 publications

References 0 publications

A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer

A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer

Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients

Analysis of EphA2 expression and mutant p53 in ovarian carcinoma

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