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Biomedical subjects

C J Dunton

Publications and source records attributed to C J Dunton.

At least 19 recordsLinked to original sources
PubMed2000

Complete response to topotecan of recurrent fallopian tube carcinoma.

OBJECTIVE: To describe the first complete response of recurrent Fallopian tube carcinoma to topotecan. METHODS: A patient with recurrent Fallopian tube carcinoma previously treated with paclitaxel (Taxol) and carboplatin is described. RESULTS: This patient demonstrated a complete clinical response to topotecan. Radiographic and CA-125 measurements were used to determine response. Response was noted after four cycles and a complete response demonstrated after six treatments. CONCLUSION: Topotecan appears active in recurrent Fallopian tube carcinoma.

Aged↗
PubMed2000

Topotecan has substantial antitumor activity as first-line salvage therapy in platinum-sensitive epithelial ovarian carcinoma: A Gynecologic Oncology Group Study.

PURPOSE: Topotecan is known to be active in recurrent ovarian cancer, but most prior studies have focused on platinum-resistant or refractory populations. This study was undertaken to define the response rate and progression-free interval in platinum-sensitive patients. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after one or two prior chemotherapy regimens and in whom the interval between prior platinum therapy and the initiation of protocol therapy was greater than 6 months were treated with topotecan 1.5 mg/m(2) intravenously over 30 minutes daily for 5 days, with this cycle repeated every 21 days. RESULTS: Forty-eight patients were entered onto the study; 47 were assessable for toxicity and 46 for response. The response rate was 33% (two complete responses and 13 partial responses), with a median response duration of 11.2 months. Hematologic toxicity predominated but was manageable in most patients with frequent incorporation of cytokines and RBC and platelet transfusions. Fatigue was reported in 15 patients and resulted in the discontinuation of therapy in five responding patients. CONCLUSION: Topotecan is an active drug in platinum-sensitive ovarian cancer, with significant but manageable hematologic toxicity. Fatigue is also a common problem that may be dose-limiting in some patients.

Adult↗
PubMed1999

Endometrial cancer in polyps associated with tamoxifen use.

We report 5 cases of carcinoma arising within tamoxifen-associated endometrial polyps. In 4 of 5 cases there were no other changes within the endometrium. Given these findings, the sonohysterographic differentiation between a polypoid structure and thickened endometrium does not eliminate the need for histologic sampling of the uterine cavity.

Aged↗
PubMed1999

Stereotactic Irradiation: potential new treatment method for brain metastases resulting from ovarian cancer.

Stereotactic irradiation (radiosurgery) is a method of precisely focusing well-defined beams of radiation at small intracranial targets. The technique has been applied to the treatment of brain lesions that are benign (e.g., arteriovenous malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas, metastases). This paper introduces preliminary data suggesting the possible value of radiosurgery in the management of ovarian cancer metastatic to the brain. Among 32 women with ovarian cancer metastatic to the brain treated with whole brain irradiation, nine (29%) experienced a complete radiographic response, compared with two of the five patients (40%) treated with radiosurgery. The 2-year survival rate was 60% among those treated with radiosurgery and 15% among those who received whole brain irradiation without radiosurgical boost. Stereotactic irradiation may be of clinical benefit to select patients with brain metastases resulting from ovarian cancer. A prospective randomized trial has been implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine whether such observations are reproducible on a national scale.

Adult↗
PubMed1999

Onycholysis associated with weekly administration of paclitaxel.

OBJECTIVE: To report an unusual reaction associated with weekly administration of paclitaxel. CASE SUMMARIES: Onycholysis was seen in four women with recurrent ovarian cancer being treated with low-dose, weekly paclitaxel. Two of the patients had previously received higher doses of paclitaxel on an every-three-week schedule without similar reactions. Onycholysis developed between weeks 10-13 of treatment in three of the patients. In the fourth patient, it developed shortly after initiation of weekly paclitaxel. None of the reactions required dose adjustments or discontinuation of therapy. Direct toxicity to the nail bed or inhibition of angiogenesis are possible mechanisms for this reaction. DISCUSSION: Onycholysis, separation of the nail from the nail bed, is an infrequent adverse effect of drug therapy. Antineoplastic drugs have previously been reported to cause onycholysis, pigmentation, bands, thickening or thinning of the nail bed, and nail shedding. Nail changes with the taxanes, primarily docetaxel, are reported in up to 30-40% of patients. Paclitaxel is not commonly associated with dermatologic reactions, although localized skin reactions and tissue necrosis have been reported. Nail changes, pigmentation or discoloration of the nail bed, occur in 2% of patients receiving paclitaxel. CONCLUSIONS: Onycholysis is an uncommon reaction that may occur in some patients receiving weekly, low-dose paclitaxel therapy. The reaction is not life-threatening and does not warrant discontinuation of therapy. However, clinicians should be aware of the possibility of this effect and be prepared to advise patients who develop signs of nail changes.

Aged↗
PubMed1998

Secondary response of ovarian tumors to topotecan treatment.

Three patients presented with ovarian cancer that was initially treated with paclitaxel and platinum-based compounds. Although responses to these agents occurred, tumor progression was evident by elevated CA 125 levels after a period of 11 to 35 months. These patients were then treated with topotecan and exhibited a response and stopped therapy. All patients subsequently had progression of disease. The patients were again treated with topotecan and have experienced favorable responses. All three patients are currently receiving treatment with topotecan and have stable disease. The results presented here suggest that re-treatment with anti-tumor agents, such as topotecan, may be able to elicit a response in tumors previously sensitive to these agents.

Adult↗
PubMed1998

Concomitant irradiation and dose-escalating carboplatin for locally advanced carcinoma of the uterine cervix: an updated report.

The combination of radiotherapy and carboplatin is associated with high response rates among women who have cervical cancer. To improve control rates for patients who have locally advanced carcinoma of the uterine cervix, oncologists have explored combinations of radiotherapy and chemotherapy. Carboplatin is an analogue of cisplatin, with similar efficacy against cervix cancer and a toxicity profile that is theoretically appealing for this group of patients because it is not nephrotoxic. Fifteen women with International Federation of Gynecology and Obstetrics (FIGO) stages IB2 through IIIB or recurrent carcinoma of the cervix were treated with megavoltage irradiation and weekly intravenous carboplatin (7 women, 60 mg/m2; 8 women, 90 mg/m2). Response was documented among all patients treated at 60 mg/m2 (three complete responses, four partial responses) and in 6 women treated with 90 mg/m2 (four complete responses, two partial responses). The two nonresponders in the series presented with recurrent glassy cell carcinoma of the cervix. All patients completed the planned course of therapy without the need for treatment interruption. At 60 mg/m2, one dose of carboplatin was withheld because of grade 2 thrombocytopenia. At 90 mg/m2, one case of grade 2 leukopenia was documented. The leukocyte counts remained within normal limits for all 3 patients who were irradiated through extended portals that encompassed the paraaortic nodes (2 women, 60 mg/m2; 1 woman, 90 mg/m2). To date, 2 of 7 patients treated at the lower dose level have died of disease (one local progression and distant failure at 11 months, one distant failure alone at 6 months). The remaining patients treated at 60 mg/m2 are alive at a median of 24 months (range, 21-37 months). Among those treated at the higher dose level, 1 patient is alive with local and distant failure at 14 months, and 1 woman succumbed to local and distant disease at 4 months. The remainder are alive at a median follow-up of 6 months (range, 2-10 months). The regimen was unsuccessful in salvaging women with recurrent glassy cell carcinoma. We conclude that the combination of radiotherapy and carboplatin can be safely delivered at both of the chemotherapy schedules studied. The regimen should not be offered to women who have recurrent glassy cell tumors. To prove the efficacy of this approach, phase III testing should be considered that compares the combination of agents to irradiation alone.

Adult↗
PubMed1998

Dilated fallopian tubes: MR imaging characteristics.

PURPOSE: To determine the magnetic resonance (MR) imaging characteristics of hydrosalpinx and the accuracy of MR imaging for distinguishing hydrosalpinx from other adnexal masses. MATERIALS AND METHODS: Cross-referencing of pathologic records and MR studies from two institutions disclosed 41 study patients with surgically proved dilated fallopian tubes. A set of 38 patients with surgically evaluated adnexal masses, but no hydrosalpinx, were randomly chosen as control subjects. All MR examinations included T1-weighted spin-echo and T2-weighted fast spin-echo imaging in multiple planes with a phased-array multicoil. Two blinded readers scored each adnexa for the presence of a dilated fallopian tube or thickened tubal wall and mucosal folds and the signal intensity of the intratubal fluid. Blinded readings were compared with surgical findings of dilated fallopian tube, endometriosis, and salpingitis. Radiologic-pathologic correlation was performed with adnexal specimens imaged in vitro in three study patients. RESULTS: On a per patient basis, the blinded readers correctly identified dilated fallopian tubes in 31 of 41 study patients and correctly excluded dilated tubes in a mean 34 of 38 control subjects. On T1-weighted images, hyperintense tubal fluid was significantly correlated with the presence of endometriosis in the pelvis at surgery (P < .002, chi 2). CONCLUSION: MR imaging can depict most dilated fallopian tubes and differentiate them from other adnexal masses on the basis of morphologic features. On T1-weighted images, high signal intensity is correlated with the presence of endometriosis affecting the tube.

Adult↗
PubMed1997

Ki-67 antigen staining as an adjunct to identifying cervical intraepithelial neoplasia.

The purpose of the work was to determine the feasibility and predictive value of Ki-67 immunostaining of cervical cytology and the detection of cervical dysplasia. Air-dried cervical smears were stained with MIB-1 antibody to identify the Ki-67 antigen. Nuclear decoration in abnormal squamous nuclei determined immunoreactivity. One hundred twenty-four nonpregnant patients underwent colposcopy and directed biopsies for abnormal cytology. Sensitivity (0.89), specificity (0.65), positive predictive value (0.60), and negative predictive value (0.91) were found for Ki-67 immunostaining in detection of high-grade cervical intraepithelial neoplasia (CIN) in 124 patients and positive Ki-67 staining was a significant predictor of high-grade CIN in both univariate (odds ratio 15.5 (95% CI 5.5-43.8) and multivariable (odds ratio 21.5 (95% CI 5.0-92.0) analysis. In 101 patients with ASCUS and LGSIL, Ki-67 immunostaining demonstrated the following in detection of high-grade CIN: sensitivity (0.96), specificity (0.67), positive predictive value (0.49), and negative predictive value (0.98). Ki-67 immunostaining of cervical cytology is a predictor of significant cervical pathology with high sensitivity and negative predictive value. Ki-67 immunostaining of cervical cytology may represent a new and cost-effective triage tool for patients with minor abnormalities on cytology.

Adolescent↗
PubMed1997

The relationship of local and distant failure from endometrial cancer: defining a clinical paradigm.

PURPOSE: Recently, statistical methods have been developed to rigorously assess the relationship between local and distant failures. Such methodology has successfully been applied to a variety of tumors including those arising in the prostate, breast, and cervix. To date, no published data are available to generate a hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of locoregional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy followed by adjuvant radiotherapy. METHODS: The series consisted of 394 patients with FIGO stages I-III endometrial cancer who were surgically staged prior to irradiation [median external beam dose 45 Gy +/- brachytherapy (median vaginal surface dose, 30 Gy)]. The duration of follow-up ranged from 2 to 151 months, with a median of 62 months. Multiple factors were evaluated to determine the associations with distant relapse including FIGO pathological stage, grade, histopathologic subtype (adeno vs papillary/papillary-serous/clear cell), depth of myometrial penetration, age, and local disease status. Time-dependent survival models were generated to assess the influence of local failure on distant metastases. RESULTS: For the entire series, the 5-year actuarial rates of local and distant failures were 9 and 20%, respectively. Women who failed locally had nearly a fourfold risk of failing distantly compared to those who remained locally controlled (P = 0.02). Moreover, the earlier a local failure developed (e.g., within 1 year vs within 3 years), the more likely it was to be associated with distant metastases (P < 0. 05). The univariate correlations of other factors with the 5-year rate of freedom from distant relapse also disclosed significant associations for grade, histology (adenoca vs papillary/papillary-serous/clear cell), and FIGO path stage. In multivariate analysis, only local control, low grade (grade 1 and 2), and early pathological stage were independently related to the likelihood of achieving freedom from distant relapse. CONCLUSIONS: Distant dissemination of endometrial cancer may develop secondary to local failure. Optimization of local control is therefore necessary if long-term cure is to be achieved. The limits of the current database cannot establish whether local failure is a cause of distant spread or a high-risk marker for metastases; however, ongoing national cooperative trials may resolve this controversy.

Actuarial Analysis↗
PubMed1997

National trends in the surgical staging of corpus cancer: a pattern-of-practice survey.

OBJECTIVE: To survey general gynecologists regarding the nature of surgical staging of corpus cancer as practiced in the United States. METHODS: A survey tool was designed to ascertain issues related to surgical staging of corpus cancer among gynecologists in the United States. The survey elicited data pertaining to the demographics and practice characteristics of the respondents. The questionnaire was sent to 700 practicing gynecologists selected randomly from the ACOG membership list. RESULTS: Responses were obtained from 227 physicians; however, only 193 could be analyzed. Most of the respondents classified themselves as general gynecologists (93%) and nonacademicians (90%). In a typical year, 60% evaluated fewer than five patients with corpus cancer. A minority of respondents carry out surgical staging of their patients, which includes total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO), removal of pelvic and para-aortic lymph nodes, and cytologic evaluation of peritoneal fluid. No uniformity was observed regarding the numeric definition of an appropriate "sampling" (median 5, range 1-25) or "dissection" (median 10, range 1-40) of lymph nodes. Most respondents would not return a corpus cancer patient to the operating room to carry out lymph node dissection if a referring colleague had performed TAHBSO but had not removed the nodes. In such a scenario, private practitioners were approximately three times less likely to reoperate on lymph nodes than academic physicians. CONCLUSION: Complete surgical staging is not performed by most physicians caring for women with corpus cancer. The relatively high proportion of nonresponders and nonevaluable responses suggests that these results should be corroborated by other investigators.

Female↗
PubMed1997

Quantitative image analysis of MIB-1 reactivity in inflammatory, hyperplastic, and neoplastic endocervical lesions.

The diagnosis of endocervical neoplasia can be difficult as it is sometimes mimicked by proliferative or reactive glands. MIB-1 is a proliferation marker that can aid in the diagnosis of squamous intraepithelial lesions (SIL) of the cervix and vulva, but its potential value in the diagnosis of endocervical lesions has not been fully explored. Ten formalin-fixed, paraffin-embedded cases of each of the following were obtained: morphologically normal endocervical glands from patients with cervical SIL, endocervicitis, microglandular hyperplasia (MGH), and endocervical adenocarcinomas (eight in situ, two invasive). Microwave unmasking of antigens was performed prior to immunohistochemical staining for MIB-1 using the avidin/biotin peroxidase method. Labeling indexes were calculated for 34 specimens (10 adenocarcinoma. 8 each of the other diagnoses) using image analysis (Samba 4000). There was diffuse MIB-1 reactivity in adenocarcinoma (labeling index 57-96%, mean 80%), minimal focal reactivity in normal glands underlying SIL (labeling index 0.8-4.3%, mean 2.4%), moderate spotty reactivity in MGH (labeling index 2.9-18.4%, mean 8.5%), and minimal to focally diffuse reactivity in endocervicitis (labeling index 1.0-13.3%, mean 5.7%). These data indicate that the percentage and distribution of MIB-1-reactive endocervical cells can be of diagnostic utility in distinguishing neoplastic glands from those of endocervicitis and MGH.

Adenocarcinoma↗
PubMed1997

New options for the treatment of advanced ovarian cancer.

Over the last decade, platinum-based combination chemotherapy regimens have led to higher response rates and longer survival for advanced ovarian cancer patients than previous regimens based on alkylating agents. The advent of paclitaxel for salvage therapy and, more recently, as a component of first-line treatment in advanced disease has further improved response rates and prolonged survival. Nonetheless, even with current treatments, relapse rates remain high and most women with advanced ovarian cancer ultimately will die of their disease. For this reason, the development of new, effective second-line treatments, as well as better first-line agents, for advanced disease remains a high priority. To maximize the efficacy of second- or third-line drugs, new agents should be non-cross-resistant with platinum or paclitaxel. Chemotherapy drugs for advanced ovarian cancer with novel mechanisms of action include topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor. Topotecan was recently shown to be effective in platinum-refractory or -resistant patients, with response rates ranging from 14% to 23%. Results from a phase III clinical study indicate that topotecan compares favorably with paclitaxel as a second-line treatment for stage III and IV patients who have failed platinum-based regimens. Moreover, a phase II study demonstrated clinical responses with topotecan in patients who had failed both paclitaxel- and platinum-based therapies. Other agents for advanced ovarian cancer are also under investigation, including docetaxel, oral etoposide, liposome encapsulated doxorubicin, gemcitabine, ifosfamide, and hexymethylmelamine.

Antineoplastic Agents↗
PubMed1996

Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent.

This study was designed to compare the effectiveness of loop excision procedures as ablation and conization equivalents, and their use in recurrent cervical high-grade dysplasia patients. We retrospectively reviewed patients undergoing loop procedures between January 1992 and April 1994. Conization equivalents were defined as procedures performed for unsatisfactory colposcopy, positive endocervical curettage, discordant cytology and histology, and cytology suggestive of invasion. Effectiveness in high-grade recurrent lesions was evaluated separately. Therapeutic failure was defined as any recurrence of high-grade dysplasia. One hundred sixty-two patients underwent loop procedures, of which 123 (75.9%) had follow-up examinations and are included. Mean follow-up was 17.9 months. Seventy-six patients (61.8%) had the loop procedure performed as an ablation equivalent, 29 (23.6%) as a conization equivalent, and 18 (14.6%) for recurrent disease. Overall effectiveness was 82.1 % and for ablation and conization equivalent procedures was 82.9 and 82.8%, respectively. There was no significant difference between effectiveness when performed for initial therapy (82.9%) and for recurrent disease (72.2%) (P = 0.46). In conclusion, loop excision procedures are effective as ablation and conization equivalents and as treatment for recurrent high-grade dysplasia.

Conization↗
PubMed1996

Percutaneous abscess drainage in gynecologic cancer patients.

Percutaneous abscess drainage (PAD) is regarded as an alternative treatment for the care of the gynecologic cancer patient with a pelvic infection. Four female patients with infected pelvic malignancies were evaluated and treated with PAD at Thomas Jefferson University Hospital over a 4-year period. Abscesses in three of the four patients were drained successfully and the catheters were ultimately removed. Successful drainage was defined as a good clinical response and avoidance of surgical debridement. For the patient with an infected pelvic malignancy, PAD offers an alternative to surgery without associated morbidity. Our experience indicates PAD is associated with expedient clinical recovery and preservation of quality of life for most patients.

Abscess↗