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C L Edwards

Publications and source records attributed to C L Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1997

Prolonged remission of platinum-refractory ovarian cancer with docetaxel: brief report and review of literature.

Platinum-based chemotherapy is the standard treatment for ovarian cancer, with response rates of 70-80%. Docetaxel has an increasing role as salvage therapy in patients with platinum-refractory ovarian cancer. In this report, we present the case of a patient with platinum-refractory ovarian cancer who achieved a long-term complete remission with docetaxel therapy. Two years after completion of chemotherapy with docetaxel, she continues to have no evidence of disease.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Remission of refractory gestational trophoblastic disease in the brain with ifosfamide, carboplatin, and etoposide (ICE): first report and review of literature.

Gestational trophoblastic disease (GTD) metastatic to the brain has a very poor prognosis with a survival rate of less than 25%, especially for patients in whom brain metastases develop while on or after chemotherapy. Cure can be achieved by chemotherapy alone. The regimen of etoposide, methotrexate, actinomycin-D, vincristine, and cyclophosphamide has shown encouraging results and is considered to be standard first-line treatment for high risk patients. For patients in whom this regimen fails, a salvage chemotherapy regimen is used. The combination of ifosfamide, carboplatin, and etoposide (ICE) has synergistic activity in preclinical studies. This regimen has shown activity in metastatic breast cancer and non-small-cell lung cancer as well as platinum-resistant germ-cell tumors and metastatic GTD. This is the first report of a patient with a highly refractory GTD in whom brain metastasis developed while on chemotherapy, and whose brain metastasis went into remission with a low dose ICE regimen. Accordingly, ICE may be considered for patients with chemotherapy refractory GTD metastatic to the brain.

Adult↗
PubMed1997

A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix.

A Phase I study of the novel angiogenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP-470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

Adult↗
PubMed1996

HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2.

This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL) in vitro in low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200-600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expanded in vitro with rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 +/- 10%) compared to tumors from which TIL failed to grow (40 +/- 10%) (P = 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 +/- 114 vs 154 +/- 20; P = 0.005) and proportions (90 +/- 3% vs 77 +/- 4%; P = 0.023) of infiltrating CD3+ cells, significantly higher numbers per field (115 +/- 44 vs 19 +/- 5; P = 0.003) and proportions (25 +/- 5% vs 11 +/- 2%; P = 0.017) of CD8+ cells and significantly higher numbers per field of CD4+ cells (318 +/- 101 vs 113 +/- 18; P = 0.025), in comparison to tumor specimens from patients whose TIL did not grow in vitro. Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r = 0.67; P = 0.005) CD3+ cells (r = 0.70; P = 0.002), CD4+ cells (r = 0.69; P = 0.003), and CD8+ cells (r = 0.82; P = 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r = 0.45; P = 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro, in low concentrations of rIL-2.

Adult↗
PubMed1996

Effects of interleukin-1 alpha on ovarian carcinoma in patients with recurrent disease.

The aim of this study was to evaluate the safety and the biological effects of interleukin (IL-1 alpha) in patients' with recurrent ovarian carcinoma treated with carboplatin. In this phase I study, IL-1 alpha was administered by a continuous intravenous infusion at doses ranging 0.1-10 micrograms/m2 every 24 h for 4 days (96 h) 3 weeks before the first dose of carboplatin (400 mg/m2) in patients with potentially platinum-sensitive ovarian cancer. The maximum tolerated dose was 3 microgram/m2/day. Dose-limiting effects at 10 micrograms/m2/day were fever, chills, hypotension and fluid retention. Minor but objective antitumour effects were observed in 2 of 18 patients. 4 patients (including 1 with a minor response) had a decrease of the CA-125 serum level ranging from 33 to 39%. The trial design precluded evaluation of the duration of response to single-agent IL-1 alpha. Based on this trial design, there is evidence of minor antitumour effect to a single course of IL-1 alpha dose given prior to chemotherapy.

Adult↗
PubMed1996

Preliminary report of the activity of docetaxel in advanced or recurrent squamous cell cancer of the cervix.

Eighteen patients with squamous cell cancer of the cervix were treated with i.v. docetaxel 100 mg/m2 over 1 h every 21 days. No patient received prior chemotherapy, except as a radiation sensitizer. Median age was 42 years (range 30-58) and Zubrod performance status was 1 (0-2). Ten (59%) patients had prior surgery and 11 (65%) had prior radiation therapy. Sixteen patients were evaluable for response. Two patients had a partial response (13%; 95% CI 0-32%) and eight (50%; 95% CI 23-77%) had stable disease. Dose reduction to 75 mg/m2 was required in 10 patients and to 55 mg/m2 in one patient. Granulocytopenia was the major hematopoietic toxicity (31% grade 3 and 44% grade 4). Docetaxel is active in patients with squamous cell cancer of the cervix and may be tolerable at this dose schedule.

Adult↗
PubMed1996

Remission of refractory gestational trophoblastic disease with high-dose paclitaxel.

High-risk metastatic gestational trophoblastic disease (GTD) in patients who have failed primary chemotherapy has a very poor prognosis. About 25% of women with high-risk metastatic disease become refractory to EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide and vincristine) and fall to achieve a complete remission. Currently, there is no standard salvage chemotherapeutic regime for EMA-CO failure. Paclitaxel, a taxane analog extracted from the bark of the western yew (Taxus brevlfolla), has shown antitumor activity in a variety of cancer cell lines. High in vivo efficacy was confirmed in phase II trials, especially for breast and epithelial ovarian cancer patients. Recently, two in vitro studies have shown that paclitaxel is a highly effective antineoplastic agent in choriocarcinoma cell lines. We present the first clinical report of a serologic remission with high-dose paclitaxel (250 mg/m2 i.v. infusion over 24 h every 3 weeks) of a highly refractory GTD in a patient who developed brain metastasis after multiple combined chemotherapeutic regimens. The patient tolerated paclitaxel with granulocyte colony stimulating factor support very well. The remission with paclitaxel in this patient confirms its preclinical activity in high-risk, refractory GTD.

Adult↗
PubMed1996

Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.

Recurrent and metastatic cervical carcinoma has very poor prognosis, mainly because there is no effective systemic therapy which would increase the duration of survival. Biologic agents have recently been found to have activity in cervical carcinoma. The combination of interferon (IFN)-alpha and 13-cis-retinoic acid had additive and synergistic antitumor activity. Both have antiviral, immunoregulatory and antiangiogenic properties, and are known to modulate malignant cell differentiation and proliferation. We report two patients with recurrent squamous cell carcinoma (SCC) of the cervix who had small-volume progressive metastatic disease, and were treated with a combination of IFN-alpha and 13-cis-retinoic acid. The first patient had pelvic lymph node metastases and the other had lung metastases. The previously progressive diseases remained stable for a prolonged period of time, 3 and 4 years, with a good quality of life. These cases suggest the possibility of using IFN-alpha and 13-cis-retinoic acid as a treatment for small-volume residual disease or as postinduction therapy in patients at high risk for disease recurrence.

Adult↗
PubMed1996

Remission of advanced uterine leiomyosarcoma with pulmonary metastases with carboplatin and paclitaxel.

A patient who had a high-grade uterine leiomyosarcoma (LMS) with extensive intra-abdominal and pulmonary metastases at the time of diagnosis underwent supracervical hysterectomy, bilateral salpingo-oophorectomy and tumor reductive surgery. She then received induction chemotherapy with paclitaxel 135 mg/m2 over 24 h and carboplatin (target AUC = 7.5 mg.ml/min) monthly for seven courses, achieving remission with a small amount of residual disease. The treatment was well tolerated except for peripheral neuropathy. Accordingly, the combination of carboplatin and paclitaxel may be considered in patients with advanced high-grade LMS of the uterus, and this regimen warrants further study in this disease.

Antineoplastic Agents↗
PubMed1996

Immunopharmacology and cytokine production of a low-dose schedule of intraperitoneally administered human recombinant interleukin-2 in patients with advanced epithelial ovarian carcinoma.

We determined in the peritoneal cavity (p.c.) of epithelial ovarian carcinoma patients during a 4-day treatment cycle of low-dose recombinant human interleukin-2 (rIL-2): (a) pharmacokinetics of IL-2, (b) endogenous cytokine production, and (c) numbers and percentages of peritoneal exudate lymphocytes. We administered 6 x 10(5) IU/m2 of rIL-2 (0.03 mg/m2 Proleukin rIL-2) intraperitoneally (i.p.) over 30 min on each of 4 days. One and one-half liters of D5 0.25 NS was injected i.p. before each rIL-2 infusion. Multiple peritoneal fluid samples were obtained from each of four patients on day 1 and day 4 for detection of IL-2, endogenous cytokines, and soluble IL-2 receptor (IL-2R-alpha). IL-2 concentrations in the peritoneal fluid were determined by bioassay and interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-10, transforming growth factor (TGF)-beta 2, and sIL-2R-alpha by enzyme-linked immunosorbent assay. Numbers of cells per microliter and lymphocyte subpopulation percentages after staining with a panel of monoclonal antibodies were determined on day 1, day 4, and subsequent off-treatment days. IL-2 disappearance in the p.c. was well described by a pharmacokinetic model having constant-rate infusion and biexponential disposition. About 90% of the IL-2 disappearance occurred during the beta-phase, during which IL-2 concentrations were sustained at approximately 10-30 ng/ml (day 1 and day 4) and the median t1/2 beta was 21.5 and 9.2 h on days 1 and 4, respectively. In four of four patients, p.c. production of IL-10 was observed on day 1 and day 4 (maximum 387 pg/ml). Maximum levels of IFN-gamma and sIL-2R-alpha were observed on day 4. (IFN-gamma 217 pg/ml; sIL2-R-alpha: 3486 U/ml). No increases in TNF-alpha or TGF-beta 2 were observed. Large increases in p.c. CD3+, CD4+, CD8+, CD16+, and CD56+ cells were observed. We conclude that biologically active levels of IL-2 are generated in p.c. fluids after i.p. administration of rIL-2 at 0.03 mg/m2.

Adult↗
PubMed1996

Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.

PURPOSE: To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. PATIENTS AND METHODS: Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months. RESULTS: Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). CONCLUSION: Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.

Adult↗
PubMed1996

Paclitaxel in patients with platinum-resistant ovarian cancer: a selected review of literature and clinical experience.

Single-agent paclitaxel infused over 24 hours produces response rates of 10 per cent to 20 per cent and 48 per cent respectively, for doses of 135 mg/m2 and 250 mg/m2. This suggests a dose response relationship. However, only a randomized trial comparing the 135 mg/m2 and 250 mg/m2 doses can confirm this result. Unfortunately, the median survival is comparable despite the difference in response rates. This may be secondary to a low CR noted at all doses. The apparent lack of benefit in terms of increased survival for the high dose group, with its attendant increase in incidence of toxic effects and cost (owing to both the paclitaxel and the G-CSF), suggest that the role of higher doses remains to be proven. It may be most useful in alleviating the severe cancer induced symptoms of some patients with advanced platinum resistant ovarian cancer(19). Despite the extensive international experience with paclitaxel in the ovarian cancer clinic its role still needs to be better defined both for salvage therapy and in combination with platinum as a front-line treatment.

Adult↗
PubMed1996

Leuprolide acetate in advanced ovarian serous tumor of low malignant potential. A case report.

BACKGROUND: Patients with advanced ovarian tumors of low malignant potential have no defined systemic therapy. Leuprolide acetate and other gonadotropin-releasing hormone analogues have definitive activity in ovarian epithelial carcinomas. On the basis of these considerations, we used leuprolide acetate to treat a young woman with an advanced ovarian tumor of low malignant potential. CASE: In a case of a long-term survivor of high-risk advanced-stage ovarian serous tumor of low malignant potential, suboptimal primary cytoreductive surgery was performed; at that time it was found that the tumor had directly invaded the outer uterine wall and rectosigmoid colon serosa and had metastasized to the pelvic lymph nodes. Postoperative adjunctive hormonal treatment with leuprolide acetate was administered and resulted in a complete clinical and serologic response. The patient remained disease free 68 months after the initial diagnosis. Her only symptoms were minimal hot flashes and vaginal dryness. CONCLUSION: Leuprolide acetate may be active in the treatment of ovarian tumors of low malignant potential. It should be considered frontline systemic therapy for this disease.

Adult↗
PubMed1996

Malignant transformation in endometriosis of the urinary bladder: case report of clear cell adenocarcinoma.

Clear cell adenocarcinoma of the urinary bladder is a very rare neoplasm. This mullerian tumor frequently arises from ovarian endometriosis. We present a case of clear cell adenocarcinoma arising from endometriosis in the bladder; this is only the third such case report in the English language literature. Endometriosis involves the bladder in only approximately 1% of patients with this disease. The patient is a 40 year-old woman who has a history of adenocarcinoma arising from endometrial tissue in the bladder. Her tumor invaded the rectum, necessitating an anterior resection of the rectum as well as a partial cystectomy and a right oophorectomy. This case confirms that the relationship between endometriosis and clear cell adenocarcinomas of the female genital tract extends to the urinary bladder. Carboplatin chemotherapy was initiated in this patient.

Adenocarcinoma, Clear Cell↗
PubMed1996

Paclitaxel retreatment in patients with platinum and paclitaxel resistant ovarian cancer.

The optimal role of paclitaxel in the treatment of epithelial ovarian cancer has not been determined. Dose intense paclitaxel therapy is safe and often recommended as second-line treatment for platinum resistant ovarian cancer. Retreatment with a higher dose-intense schedule of paclitaxel is feasible and patients who had a prior dose of 135 mg/m2 or paclitaxel free interval of at least six months may respond. Sensitivity to initial doses and a prolonged paclitaxel-free interval are predictors of a successful reinduction. We report 10 patients who had paclitaxel as second-line treatment and were later retreated with paclitaxel. Three of these patients had a partial response (30%; 95% CI 6-66%). All but one patient had platinum resistant disease. Initial dose and the best response to initial paclitaxel were assessed in relation to reinduction response. Patients with at least a six-month paclitaxel-free interval and previously low dose paclitaxel (135 mg/m2), or a complete response with high dose paclitaxel (250 mg/m2) may respond to high dose paclitaxel retreatment. Prospective trials of paclitaxel retreatment are warranted.

Adult↗
PubMed1996

A case report of paclitaxel administered to a patient with platinum-refractory ovarian cancer on long-term hemodialysis.

We present the second case of a patient with platinum-refractory ovarian cancer who was treated safely with paclitaxel while on hemodialysis. Paclitaxel was administered at 175 mg/m2 as a 24-hour intravenous infusion on a nondialysis day. The patient tolerated this therapy well with minimal toxic reactions except for total alopecia and myelosuppression, which was unremarkable. Paclitaxel may be used in patients receiving long-term hemodialysis in the same dose schedule as in patients with normal renal function.

Adult↗
PubMed1996

Vulvar intraepithelial neoplasia and vulvar cancer.

Vulvar carcinoma is a rare cancer. It is more frequent among older women, but the incidence is increasing among younger women. The incidence of VIN may be rising in younger women as well. Different factors have been associated with an increased risk for vulvar cancer (HPV, age, smoking, education, diet, genital infections, infrequent pelvic examinations, socioeconomic status, immunosuppressive diseases); however, conclusive epidemiologic evidence is lacking. More studies with larger sample sizes are needed to understand more fully the role of these and other as yet unknown factors in the etiology of vulvar cancer. At present, studies of the molecular risk assessment for VIN and vulvar cancer focus mostly on HPV. The treatments for VIN are painful, and the disease has a high risk of recurrence. The treatments for vulvar cancers are morbid, even though radical vulvectomy is being replaced by the less morbid wide local excision and unilateral groin lymph node dissection. Therefore, VIN and vulvar cancer benefit from early detection, and their morbidity is decreased by early treatment. Screening should be performed by the primary care practitioner and should focus on women with HPV; women who smoke; and women who have other preinvasive disease of the cervix, vagina, or perianal area. Chemoprevention and an HPV vaccine may eventually be promising, but no studies have yet been performed. Patients should be educated about performing vulvar self-examination stopping smoking, being persistent about insisting on a biopsy if symptoms persist, and avoiding exposure to HPV.

Biomarkers, Tumor↗