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J T Chambers

Publications and source records attributed to J T Chambers.

At least 37 records · Page 2Linked to original sources
PubMed1996

Phase I trial of intravenous carboplatin and cyclosporin A in refractory gynecologic cancer patients.

Our objective was to determine the maximum tolerated dose of cyclosporin A (CsA) delivered as a loading dose (LD) and continuous i.v. infusion (CI) in combination with carboplatin in patients with refractory gynecologic cancers. Twenty-nine heavily pretreated patients (25 ovarian epithelial, 2 cervical, and 2 endometrial carcinomas) received 113 cycles of CsA and carboplatin from September 1989 to September 1991. Twenty-four of these 29 carcinomas were strictly defined to be platinum resistant. CsA was administered as a LD escalated from 6 to 10 mg/kg followed by a 24-h CI from 2.5 to 14.5 mg/kg/day. Carboplatin was targeted to an area under the time versus concentration curve (AUC) of 6 mg/ml x min and was not dose escalated. Whole-blood CsA concentrations (fluorescence polarization immunoassay) at the maximum tolerated dose (10 mg/kg LD, 14.5 mg/kg/day CI) ranged from 2.4 to 3.0 microgram/ml over 12 h. Estimated median carboplatin AUC, based on calculated carboplatin clearance, was 7.9 mg/ml x min. The dose-limiting toxicity of the combination of CsA and carboplatin was grade 4 thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 35% of the patients, which could be explained by the effects of carboplatin (AUC of 6 mg/ml x min) alone. Overall, neutropenia occurred in 24% of the patients and anemia in 17% of the patients. Grade 3 or 4 nausea or vomiting was noted in 10 and 14% of the patients, respectively. Grade 3 hypertension during CsA administration occurred in 14% of the patients. No grade 3 or 4 nephrotoxicity was seen in this trial. Three objective responses were noted: one complete response (11 months) and one partial response (5 months), both in potentially platinum-sensitive patients with platinum-free intervals of only 9 months each. One platinum-resistant patient had a partial response for 21 months. Five additional patients experienced >75% reduction of CA-125 or a return to a normal CA-125 titer. We concluded that whole-blood CsA concentrations of >3.0 microgram/ml (as seen when CsA is used as a modulator of multidrug resistance) were not achievable in this combination with carboplatin in this population of heavily pretreated gynecologic cancer patients. However, because CsA is used in this trial as a chemosensitizer in platinum-sensitive tumors and as a chemomodulator of platinum resistance, we targeted a CsA concentration of >1.0 microgram/ml, which was achieved. The CsA dose recommended for a Phase II trial of this combination is 10 mg/kg LD and 11.6 mg/kg/day CI, which results in blood CsA concentrations ranging from 1.2 to 1.3 microgram/ml over 12 h. Responses in this population of refractory gynecologic cancer patients are unusual, and these encouraging results form the basis for a Phase II trial of this combination.

Anemia↗
PubMed1995

Early detection and screening for ovarian cancer.

Ovarian cancer is associated with postmenopausal women of North American or European descent, nulliparous women, and women with a first-degree relative with an epithelial ovarian cancer. Methods for early detection of ovarian cancer are the pelvic examination, ultrasound techniques, and CA-125 monitoring, none of which are highly sensitive or specific for the disease. At the Yale-New Haven Medical Center, first-degree relatives of women with epithelial ovarian cancer were invited to participate in an intense ovarian cancer screening program consisting of tumor markers, endovaginal ultrasound and color Doppler flow studies, and physical examinations performed in a serial fashion. The false-positive rate for the tumor markers varied from 2 to 9% at initial evaluation of the first 247 participants. Endovaginal ultrasound and color Doppler flow techniques were used to evaluate 326 ovaries in 169 women. Resistive indices < 0.5 were present in 26 ovaries (8.4%), and peak systolic velocities > 30 cm/sec occurred in 7 ovaries (2.3%). To date, four breast cancers have been detected, three cervical intraepithelial neoplasias have been identified, and three atypical adenomatous hyperplasias were diagnosed. No epithelial ovarian cancer was found. Isolated screening for ovarian cancer even in high-risk women is not cost effective. Women screened for ovarian cancer should also be evaluated for cancers of the breast, cervix, colon, rectum and endometrium. Isolated abnormal screening test values are not an indication for surgery.

Biomarkers, Tumor↗
PubMed1995

Extramammary Paget's disease of the vulva.

Fourteen patients with extramammary Paget's disease of the vulva treated at Yale-New Haven Medical Center from 1982 through 1993 were reviewed to evaluate the accuracy of methods used to delineate surgical margins and to determine if radical operations or surgical margin status was associated with likelihood of recurrence. These 14 patients underwent at total of 25 operations for extramammary Paget's disease. In 8 operations, a total of 44 separate frozen-section biopsies were performed to determine extent of disease with a mean of 5.5 biopsies per patient. Visual judgment alone was used to determine margin status in 17 operations. The ability to delineate free surgical margins on permanent sections was not different, whether judged visually or by frozen-section analysis. Frozen-section analysis was misleading in 3/8 (37.5%) cases, while visual judgment was in error in 6/17 (35%) cases. Moreover, permanent margin status was not found to be predictive of disease recurrence. Two of 5 (40%) patients with positive margins recurred after initial surgery compared with 3 of 9 (33%) patients with negative margins. Of the 14 primary operations, there were 8 wide local excisions, 3 simple vulvectomies, and 3 modified radical vulvectomies. The radicality of the operation as initial treatment did not statistically correlate with disease recurrence.

Female↗
PubMed1995

A phase II study of etoposide, cisplatin, and doxorubicin chemotherapy in mixed müllerian tumors (MMT) of the uterus.

Mixed Müllerian tumors (MMT) of the uterus are aggressive entities that result in a very poor prognosis even for patients in whom the disease is limited to the uterus. This phase II trial was undertaken in an attempt to improve overall survival as well as progression-free survival of these patients. Forty-two consecutive patients were treated with a combination chemotherapy containing etoposide 100 mg/m2 on Days 1 and 2, cisplatin 50 mg/m2 on Day 1, and doxorubicin 50 mg/m2 on Day 1, repeated every 28 days. There were 23 patients with early-stage disease (stages I and II) and 19 patients with advanced (stages III and IV) or recurrent disease. In the early-stage group, the number of cycles ranged from 2 to 9 (5.2 +/- 1.9). The median follow-up was 32 months (range 11-93). There were five recurrences: three patients died of disease at 11, 36, and 51 months, and two patients are still alive with disease at 12 and 19 months. Two-year overall survival was 92%. In the advanced disease group, the number of cycles ranged from 1 to 11 (5.9 +/- 2.4). The median follow-up for this group was 20 months (range 5-62). The median overall survival was 18 months. Two-year overall survival was 33%. Two-year progression-free survival was 20%. Four patients were evaluable for response. There were two complete responses (duration 15-33 months) and two partial responses (duration 6-10 months). The responders were patients whose adenocarcinoma component was of the papillary serous (UPSC) variety. The chemotherapy combination appears to be highly active in early-stage disease. In the advanced uterine MMT it has moderate activity, especially when associated with the UPSC component.

Aged↗
PubMed1995

Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival.

Clear cell carcinoma (CCC) and uterine papillary serous carcinoma (UPSC) are aggressive variants of endometrial carcinoma that may coexist or share some clinicopathologic features suggesting a similar biologic spectrum and the need for a common therapeutic approach. Twenty-nine cases of pathologic FIGO stage I and II CCC and 47 cases of FIGO stage I and II UPSC seen and treated at Yale-New Haven Hospital were reviewed, and the survival rates with regard to various pathological parameters were compared. Both groups of patients had similar clinical profiles with respect to presentation, age, weight, and medical problems. The 5-year survival for pathologic stage I patients with CCC was 72% and for those with UPSC 44%. The 5-year survival for pathologic stage II patients with CCC was 59% and for those with UPSC 32%. Analysis of survival showed that the depth of myometrial invasion, the presence of vascular space invasion, and the admixture of endometrioid features did not influence survival in either group of patients. In CCC, survival was also not influenced by the predominant histologic pattern, i.e., papillary versus nonpapillary. The results of this study suggest that early stage CCC and UPSC have similar clinicopathologic profiles, suggesting the need for aggressive approaches including a staging laparotomy and possibly similar therapy. However, the stage I CCC patients had a significantly better survival than the stage I UPSC patients.

Adenocarcinoma, Clear Cell↗
PubMed1995

Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with MR imaging. Work in progress.

PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging to determine the depth of myometrial invasion in patients with clinical stage I endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length, tumor signal intensity, appearance of the junctional zone, presence of large polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB, and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep myometrial invasion (stage IC) from superficial disease (stages IA and IB) was 78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors (P = .025), and difficulty in pathologic staging (P < .005) were significantly associated with incorrect MR assessment. CONCLUSION: When present, large polypoid tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal anatomy may make it difficult to assess myometrial invasion at MR imaging.

Aged↗
PubMed1994

Prognostic indicators for poor risk epithelial ovarian carcinoma.

BACKGROUND: The objective of this study was to identify factors that categorize patients with epithelial ovarian carcinoma into favorable and unfavorable prognostic groups at the time of initial treatment. METHODS: Data were analyzed from 51 women who were treated at Yale University, had an evaluable CA 125 half-life (t1/2), and were followed for disease recurrence for at least 2 years. RESULTS: Grade, maximum level of CA 125, and histology did not provide useful prognostic information. Stage, residual disease, minimum CA 125, and CA 125 t1/2 individually were predictive of persistent disease or recurrence within 3 years of diagnosis with sensitivities of 97, 70, 34, and 49%, respectively, and specificities of 33, 83, 100, and 83%, respectively. When these factors are combined, defining an unfavorable prognostic group as those patients having residual disease greater than 1 cm, CA 125 t1/2 greater than 12 days, or minimum CA 125 never falling below 35 U/ml, sensitivity and specificity were 96 and 65%, respectively, at 1 year of follow-up and 91 and 75%, respectively, at 3 years of follow-up. 75%, respectively, at 3 years of follow-up. CONCLUSIONS: In those patients in whom residual small volume disease after primary surgery indicates a good prognosis, minimum CA 125 and CA 125 t1/2 during chemotherapy can further categorize patients into favorable and unfavorable prognostic groups.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Neoadjuvant chemotherapy for advanced ovarian cancer.

The purpose of this study was to compare the survival of women with clinical, radiologic, and histologic findings compatible with advanced ovarian cancer who were treated with neoadjuvant chemotherapy to that of a group of women with FIGO stage IIIC (suboptimal debulking) and stage IV epithelial ovarian cancers treated with the same chemotherapy. Eleven women with physical, radiologic, and histologic findings compatible with advanced ovarian cancer (median age, 73 years) treated with neoadjuvant carboplatin and cyclophosphamide chemotherapy were compared to 18 women (median age, 60 years) who had stage III and suboptimal surgical cytoreduction (> 2 cm residual tumor, 13 patients) or stage IV (5 patients) ovarian cancer followed by the same chemotherapy. The progression-free survival for the 11 women receiving neoadjuvant chemotherapy was 9.1 months which was not statistically different from the 8.5 months progression-free survival for the 18 women with suboptimally debulked stage IIIC or stage IV disease (P = 0.98). The overall survival was not significantly different (P = 0.26). Neoadjuvant-treated patients tended to tolerate chemotherapy better as none required dose reduction for bone marrow suppression, while 6 of 18 conventionally treated patient required dose reductions. In conclusion, neoadjuvant chemotherapy appears to be an effective means of palliating women with clinical, radiological, and histologic findings compatible with advanced ovarian cancer. A prospective study is necessary in which women with findings compatible with advanced ovarian cancer that is not likely to be effectively cytoreduced surgically are randomized to either undergo cytoreductive surgery followed by chemotherapy or receive neoadjuvant chemotherapy.

Adult↗
PubMed1994

Chemotherapy of recurrent/advanced cervical cancer: results of the Yale University PBM-PFU protocol.

Chemotherapy for cervical cancer patients with recurrent and/or advanced disease has been complicated by excessive toxicity and short duration of responses, leading to little or no improvement in survival. Modification of drug scheduling and delivery of platinum, bleomycin, methotrexate, and 5-FU has resulted in a new combination regimen with little toxicity and a survival advantage for responders. PBM (platinum 80 mg/m2 D1, bleomycin 10 mu/m2/day D3-6, methotrexate 150 mg/m2 D15, 22 with leucovorin) is alternated with PFU (platinum 100 mg/m2 D1, 5-FU 1000 mg/m2/day D2-5) q 4 weeks for 3-6 months. The platinum, bleomycin, and 5-FU were delivered by continuous infusion. Twenty-three patients with recurrent and 17 with advanced cervical cancer are evaluable; 91% of patients with recurrent disease had received prior radiation therapy. The response rate was 30.4% in those with recurrent disease, and 41.2% in those with advanced disease, with 86 and 42.9% of responders respectively achieving a CR. Survival data were analyzed for each group separately, as well as for the combined recurrent/advanced disease group (N = 40). The results and significance were not changed by the groupings. In the combined recurrent/advanced group, median duration of response was 10.5 months, mean 20.1, and the median overall survival was 11 months, mean 20.5 +/- 3.5. There was a survival advantage accrued to the responders (median, 28 months) vs the nonresponders (10 months) (P = 0.0005 by log rank test). Moreover, there was a significant difference in progression-free interval between responders vs nonresponders (P = 0.0001), as well as between responders and those with stable disease (P = 0.001). This regimen was very well tolerated and there was no significant pulmonary toxicity. Furthermore, in the subset of 23 patients who had recurrent disease, 67% achieved palliation of pain. Experience with this protocol supports the continuing use of chemotherapy in the management of cervical cancer patients.

Adult↗
PubMed1993

Allelic loss in ovarian cancer.

Loss of heterozygosity (LOH) was examined at 86 loci distributed on every chromosomal arm in 50 human ovarian tumors. Frequent allele losses were observed on chromosomes 13q (42%), 17p (42%), 17q (45%), and Xp (41%). Deletion mapping on chromosome 17 revealed a candidate gene on the long arm distal to D17S41/S74 for ovarian cancer which is distant from the locus for early onset breast cancer. LOH on chromosome 17q was found to be concordant with LOH on chromosomes 3p, 13q, 17p and Xp suggesting that it may be an early event in neoplastic development. These findings indicate that multiple tumor-suppressor genes for ovarian cancer possibly exist on chromosomes 13q, 17, and/or Xp and provide the basis for the identification of candidate gene(s) associated with ovarian cancer. The chromosomal mechanisms resulting in allele losses in ovarian cancer include deletion, deletion/duplication, mitotic recombination and monosomy, in concordance with the developed genetic model.

Alleles↗
PubMed1993

Intravenous cisplatin, doxorubicin, and cyclophosphamide in the treatment of uterine papillary serous carcinoma (UPSC).

Thirty patients with uterine papillary serous carcinoma were treated with intravenous cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy, a combination with proven efficacy against ovarian carcinoma. Nineteen patients were given CAP as an adjuvant soon after surgery. Eleven patients were treated after recurrence or failure of other first-line therapy. Of the patients treated adjuvantly, 11 (58%) were alive without evidence of disease with a median follow-up of 24 months. Eight patients (42%), all with metastatic disease at diagnosis, were dead of disease (DOD) with a median survival of 14 months. In the salvage group, all patients were DOD with a median survival of 21 months from diagnosis and a median survival from initiation of CAP of 7 months. Toxicity was observed in all patients, and there was one treatment-related death from cardiotoxicity. In the salvage group there were two partial responses and one complete response (response rate = 27%). We conclude that intravenous CAP was ineffective in the treatment of metastatic or recurrent uterine papillary serious carcinoma, but deserves study as an adjuvant in patients without metastatic or with only microscopic extrauterine disease.

Aged↗
PubMed1993

Colony-stimulating factor-1 in primary ascites of ovarian cancer is a significant predictor of survival.

OBJECTIVE: Our purpose was to determine whether the concentration of colony-stimulating factor in ascites of ovarian carcinoma is a prognostic factor for survival. STUDY DESIGN: Forty-four ascites samples from patients undergoing primary surgery for ovarian carcinoma were measured for colony-stimulating factor-1 by radioimmunoassay. Retrospective analysis of clinical data allowed comparison of accepted prognostic factors to ascites colony-stimulating factor-1 concentration for impact on survival by means of life-table analysis (Kaplan-Meier) by the Wilcoxon test and the Cox regression methods. RESULTS: In patients with advanced disease (International Federation of Gynecology and Obstetrics stages III and IV, n = 37) ascites colony-stimulating factor-1 concentration levels below a critical cutoff of 8.59 ng/ml were associated with longer overall survival (p < 0.05) and were a better predictor of survival than any other prognostic factor except zero residual disease after cytoreduction. International Federation of Gynecology and Obstetrics stage, tumor histologic type, malignant cells in fluid, grade of tumor, age, and performance status at presentation were not predictive of outcome. CONCLUSION: Colony-stimulating factor-1 in ascites may be an independent indicator of prognosis in patients with epithelial ovarian cancer.

Adult↗
PubMed1992

Uterine papillary serous carcinoma: a study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma.

One hundred eight cases of uterine papillary serous carcinoma (UPSC) were analyzed to characterize its histologic features and biologic behavior. Special situations that could conceivably modify the behavior and therapeutic approaches were considered: (1) the occurrence of areas of endometrioid carcinoma in otherwise typical UPSC; (2) the confinement of UPSC to an otherwise benign endometrial polyp or the endometrial mucosa or absence of residual tumor at the time of hysterectomy; and (3) the coexistence of a superficial UPSC and a serous ovarian carcinoma. There was coexistence of endometrioid and UPSC in 22 cases, and tumor was confined to an endometrial polyp or endometrium in 19 cases. There was simultaneous pathologic stage I UPSC and papillary serous ovarian carcinoma in 10 cases. In patients with pathologic stages I and II UPSC the presence of areas of endometrioid carcinoma intermixed with the UPSC did not improve survival. Patients with stage I disease and no residual tumor or tumor confined to an endometrial polyp/endometrial mucosa and without vascular invasion had a survival not statistically different from those with stage I disease but with myometrial and/or vascular invasion. Patients with stage I UPSC with concomitant ovarian serous surface papillary carcinoma had survival not statistically different from patients with stage IV UPSC.

Adenocarcinoma↗
PubMed1992

Intraabdominal hemorrhage with pulmonary large cell carcinoma metastatic to the ovary.

Secondary tumors comprise nearly 10% of ovarian malignancies; however, metastatic cancers arising from the lung are uncommon, with fewer than 15 cases reported. A patient with pulmonary large cell carcinoma and ovarian metastases resulting in recurrent refractory intraabdominal hemorrhage is presented. Metastatic involvement of the ovary from pulmonary malignancy is reviewed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Endometrial sampling: When? Where? Why? With what?

Today, evaluating women with abnormal uterine bleeding generally is initiated in the office with an endometrial biopsy. The indications and contraindications for endometrial sampling along with situations which do not, per se, demand sampling are listed in Figure 1. In women younger than 40 years of age, it may be appropriate in some clinical situations to initiate hormonal therapy after an endocrine evaluation before endometrial sampling; however, with the newer sampling devices that cause minimal discomfort, a histologic evaluation can be performed easily. Furthermore, the endometrial biopsy may help to distinguish anovulatory from ovulatory bleeding and exclude a hyperplastic condition or carcinoma. If the patient does not respond to medical therapy, then hysteroscopy may identify endometrial polyps or submucosal myomas. Bleeding in postmenopausal women requires endometrial sampling. If a diagnosis of cancer can be made in the office, this will expedite treatment. For those cases in which, for technical reasons, it is impossible to do an office biopsy or in which an examination under anesthesia is necessary for evaluation, then a D&C is indicated. The refined technology of transvaginal ultrasonography and hysteroscopy in the future may influence more directly the evaluation of women with abnormal uterine bleeding. As noted, transvaginal ultrasonography may determine which women would benefit from an endometrial biopsy, both for symptomatic and asymptomatic women. Likewise, the hysteroscope, under certain circumstances, may help identify pathologic findings missed by endometrial biopsy and/or reassure the patient or physician that a negative biopsy is the result of an atrophic mucosa. Because of the increase in the use of hormonal therapy, both in postmenopausal women for replacement and in women with breast cancer as adjuvant therapy, endometrial sampling must be performed for screening. Follow-up for women with premalignant changes of the endometrium treated with hormones also would require sampling to assess response. The overwhelming arguments in favor of the accuracy of an office-based endometrial biopsy, the convenience to the patient and physician, and the cost containment have been established firmly in the literature. Office screening procedures will continue to play important roles in the diagnostic skills of the gynecologist.

Biopsy↗
PubMed1991

Endometrial carcinoma with trophoblastic differentiation. An aggressive form of uterine cancer.

Three cases of poorly differentiated endometrial adenocarcinoma showing trophoblast-like differentiation are reported. The multinucleated, syncytiotrophoblast-like cells were strongly positive for beta-human chorionic gonadotropin (beta-HCG) by immunohistochemical study. High levels of beta-HCG were also present in the patients' serum, but dropped significantly after treatment. The patients had an unusually rapid and progressive clinical course with widespread dissemination and death by tumor.

Adenocarcinoma↗