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Biomedical subjects

E A Surwit

Publications and source records attributed to E A Surwit.

At least 55 records · Page 3Linked to original sources
PubMed1988

Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration.

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second-look laparotomy. As in many other investigations, several factors have been analyzed for predicting second-look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P less than 0.001) were significantly associated with the absence of disease at second-look laparotomy, and both were significant predictors of second-look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second-look laparotomy diminished, however. Actuarial survival after second-look laparotomy was associated with residual tumor size at second-look surgery (P = 0.02). According to second-look findings, the 3-year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% +/- 13.4% 3-year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% +/- 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% +/- 11.4% survival. We also examined the effect of extensive tumor resection at second-look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P less than 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second-look laparotomy.

Actuarial Analysis↗
PubMed1988

A phase II trial of mitomycin, vincristine, bleomycin, and cisplatin (MOBP) as neoadjuvant therapy in high-risk cervical carcinoma.

Twenty patients with locally advanced or metastatic cervical carcinoma were treated with mitomycin, vincristine, bleomycin, and cisplatin (MOBP), prior to radiotherapy (RT) of curative intent. Five patients had stage I disease, 2 stage II, 10 stage III, and 3 stage IV. All but one patient with stage I and II disease had nodal metastases. Patients received two courses of MOBP prior to and cisplatin q 3 weeks during RT. Response rates after completion of MOBP and prior to RT were as follows: 3/18 (16.6%) patients had a complete response (CR), 10/18 (55.5%) had a partial response (PR), 3/18 (16.6%) had improvement, and 2/18 (11.1%) had no response (NR). Five patients developed radiation complications. Of 7 patients with stage I and II disease, 6 (86%) currently have no evidence of disease (NED) (median 27 months). Of 13 patients with advanced disease, 3 (23%) are NED (median 17 months), 8 (61.5%) have expired, and 2 (15.4%) are alive with disease. MOBP is associated with significant response rates in the untreated patient but has not improved survival in patients with advanced disease. Patients with early disease and positive nodes may benefit from this regimen.

Adenocarcinoma↗
PubMed1988

Phase II study of fludarabine phosphate (NSC-312887) in patients with advanced ovarian cancer. A Southwest Oncology Group Study.

Fourteen evaluable patients with advanced ovarian cancer refractory to one prior chemotherapy regimen were treated with a 5-day schedule of fludarabine phosphate. No responses were noted. The major toxicity was granulocytopenia with 50% of patients having granulocyte counts of less than 1,000/microliter. Based on this study and one other previously published trial, fludarabine phosphate does not appear to be an active agent for patients with refractory ovarian cancer.

Adult↗
PubMed1988

Phase II trial of mitomycin C plus 5-FU in the treatment of drug-refractory ovarian cancer.

Following cisplatin combination chemotherapy for advanced epithelial type ovarian cancer, response to subsequent treatments has proved relatively poor. Mitomycin C and 5-fluorouracil (5-FU) have both been reported to have useful activity as single agents in patients with drug-refractory ovarian cancer. We have carried out a phase II trial of a combination of these two agents in 25 patients who had previously received a median of two chemotherapy regimens (range, one to five regimens). Patients received mitomycin C, 10 mg/m2 intravenously (IV) on day 1 every 6 weeks, and 5-FU, 500 mg/m2 IV daily on days 1 to 3 every 3 weeks. Four patients experienced a complete response and six patients a partial response, for an overall objective response rate of 40%. The median duration of complete and partial responses was 8 and 4 months, respectively. The median duration of survival for all 25 patients was 10.5 months (range, 2.5 to 49+ months). The most prevalent toxicity was bone marrow suppression. Leukopenia occurred in 68% of the patients, and 36% experienced thrombocytopenia. Severe or life-threatening bone marrow suppression was observed in 36% of the patients and required dose reduction or drug discontinuance in 28% and 24%, respectively. We conclude that mitomycin C plus 5-FU combination therapy appears to be extremely active in patients with drug-refractory disease. Confirmatory trials are indicated.

Adult↗
PubMed1988

Intraperitoneal mitomycin C in the treatment of peritoneal carcinomatosis following second-look surgery.

Persistent or recurrent peritoneal carcinomatosis (PC) documented at second-look surgery has proved relatively refractory to second-line therapy. The majority of these tumors do not respond to cisplatin based chemotherapy. Because of the relatively high response rate we observed with systemically administered mitomycin C plus 5-fluorouracil, we initiated a trial of intraperitoneal (IP) mitomycin C (10 mg/m2 in 2 L dialysate fluid every 4 weeks) in 14 patients with refractory PC secondary to gynecologic malignancies. All but one patient had PC secondary to ovarian cancer documented at second-look cytoreductive surgery following intense cisplatin based drug therapy. One patient had endometrial cancer and had been treated previously with radiation. In all, 49 courses of intraperitoneal mitomycin C were administered to 14 patients. Systemic toxicity was minimal, except for mild thrombocytopenia that occurred in four patients. However, abdominal pain due to chemical peritonitis was cumulative and dose limiting after three to five courses of therapy. Of the seven patients with measurable disease (positive serum CA-125 or intraperitoneal cytology), six had normalization of at least one of these two parameters. Eight of the 14 patients remain alive without clinical evidence of disease with a median follow-up duration of 10 months. We conclude that IP mitomycin C is a well-tolerated and potentially effective treatment modality in patients with limited PC following second-look surgical debulking for gynecologic malignancy.

Adenocarcinoma↗
PubMed1987

Tamoxifen therapy in recurrent epithelial ovarian carcinoma.

Thirty-seven patients with recurrent epithelial ovarian carcinoma were entered into a trial of tamoxifen therapy (10 mg BID) to determine the effect on long-term survival. Thirty-one patients were evaluable with follow-up ranging from 6 to 42 months since initiation of hormonal therapy. All patients were heavily pretreated with multiple chemotherapeutic regimens (median 3). There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four patients are dead (23 from advanced carcinoma, 1 from cardiac causes); 5 patients are alive with disease; 2 patients are lost to follow-up. Median survival of nonresponders was 7 months versus 16 months for responders (CR + PR + stable disease) (P = 0.001 life table analysis). Of the 9 responders, 7 had poorly differentiated tumors (grades 3 or 4), and 2 had moderately differentiated tumors (grade 2). Eleven patients had estrogen and progesterone receptor studies (ER, PR). No correlation between response rate and receptor status was evident. We conclude that although significant disease regression is unlikely to result from tamoxifen therapy, there may be a subset of patients who can benefit from the cytostatic properties of hormonal manipulation.

Carcinoma↗
PubMed1987

Phase II trial of vinblastine in previously treated patients with ovarian cancer: a Southwest Oncology Group Study.

Sixty-eight patients with relapsing, epithelial type ovarian carcinoma were entered into a Phase II study of vinblastine. Vinblastine was administered as a continuous intravenous infusion over five days at a starting dose of 1.7 mg/m2/day every 3 weeks. There were 44 fully evaluable and 6 partially evaluable patients. Forty-one of these patients had had only one prior treatment regimen. Grade 3 or 4 leukopenia occurred in 12 patients (24%), but Grade 3 or 4 thrombocytopenia occurred in only 2 patients. There were two clinical complete responses of 18 and 36 weeks duration and one partial response of 6 weeks for an overall response rate of 7%. We conclude that vinblastine, administered in optimal dose and schedule, has little clinical activity in previously treated patients with ovarian cancer.

Drug Evaluation↗
PubMed1987

Interstitial parametrial implants in carcinoma of the cervix stage II-B.

This retrospective analysis has been undertaken to ascertain whether an improvement in results can be obtained in Stage II-B cervical carcinoma with the use of interstitial parametrial irradiation. Between September 1972 and March 1982, 43 patients were treated by conventional intracavitary irradiation. Nine patients at high risk for local recurrence underwent post-radiation hysterectomy. Since 1980, 45 patients were entered into a study using parametrial interstitial implants and no hysterectomy. Patients were not allocated randomly and the interstitial group contained a disproportionate number of patients with poor prognostic features. Mean follow-up for the conventional radiotherapy group was 80 months, and for the interstitial group was 42 months. Overall pelvic control and actuarial survival in the conventional radiotherapy group (84 and 75%, respectively) were similar (log rank p-value = .61) to that observed in the interstitial implant group (80 and 77%). Analysis of pelvic control rates showed no significant advantage for either treatment group when compared by the various prognostic factors. The frequency of complications, however, was significantly higher in the interstitially irradiated patients (21% vs. 7%, p = .044).

Adenocarcinoma↗
PubMed1987

Phase II trial of vinblastine in previously treated patients with ovarian cancer: a Southwest Oncology Group Study.

Sixty-eight patients with relapsing, epithelial type ovarian carcinoma were entered into a Phase II study of vinblastine. Vinblastine was administered as a continuous intravenous infusion over 5 days at a starting dose of 1.7 mg/m2/day every 3 weeks. There were 44 fully evaluable and 6 partially evaluable patients. Forty-one of these patients had had only one prior treatment regimen. Grade 3 or 4 leukopenia occurred in 12 patients (24%), but Grade 3 or 4 thrombocytopenia occurred in only 2 patients. There were two clinical complete responses of 18- and 36-week durations and one partial response of 6 weeks for an overall response rate of 7%. We conclude that vinblastine, administered in optimal dose and schedule, has little clinical activity in previously treated patients with ovarian cancer.

Adult↗
PubMed1987

Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study.

Cisplatin has proven to be the most active single agent in the treatment of metastatic and recurrent squamous cell cancer of the cervix. In a previous southwest Oncology Group (SWOG) pilot study, the addition of cisplatin to a mitomycin-C, vincristine, and bleomycin (MVB) regimen resulted in a relatively high percentage of durable complete responses. To gain more experience with cisplatin-based chemotherapy regimens, the SWOG initiated a phase II randomized trial of cisplatin, mitomycin-C plus cisplatin (MC), and MVB plus cisplatin (MVBC) in 119 patients with advanced squamous cell cancer of the cervix and no prior chemotherapy exposure. Because of slow patient accrual early in the trial, the cisplatin arm was discontinued. Five patients were declared ineligible according to protocol criteria. The three treatment groups were relatively well matched for age, prior radiation exposure, and sites of measurable disease. The overall objective response rates for cisplatin, MC, and MVBC treated patients were 33%, 25%, and 22%, respectively. Median response durations were greater than 6 months. Median survival durations associated with cisplatin, MC, and MVBC treatment were 17.0, 7.0, and 6.9 months, respectively. There were no drug-related deaths. Severe or life-threatening leukopenia and thrombocytopenia were observed in 18% to 24% of patients treated with MVBC and MC, but in none of those receiving cisplatin alone. We conclude that the low response rates and short durations of both response and survival observed in patients randomized to the two chemotherapy combinations suggest that only enhanced toxicity was gained through the addition of mitomycin-C or MVB to cisplatin in patients with advanced cervix cancer.

Adult↗
PubMed1987

Management of high-risk gestational trophoblastic disease.

Traditionally in the United States, women have been categorized as having high-risk gestational trophoblastic disease on the basis of traditional risk criteria and have been treated in a similar fashion at most centers. Utilizing more objective and specific scoring systems allows an analysis of the most recently reported results of the treatment of high-risk patients. Identification of the "ultra-high-risk" patient allows a comparison of various therapeutic regimens at different centers. Such an analysis demonstrated the inadequacy of the traditional methotrexate/actinomycin-D/chlorambucil and modified Bagshawe regimens for these patients. Superior results have been achieved utilizing alternative regimens that include VP-16, the most effective new agent.

Adult↗
PubMed1986

A phase I trial of topically applied trans-retinoic acid in cervical dysplasia-clinical efficacy.

Forty-two patients were entered into a phase I trial to evaluate the vitamin A derivative, trans-retinoic acid, in cervical intraepithelial neoplasia. Treatment consisted of four consecutive 24-h applications of retinoids via an inert collagen sponge in a cervical cap. Patients were followed for response at 3-month intervals using cytology, colposcopy, and selected biopsies. Thirty-six patients were evaluable (mild dysplasia, 13; moderate dysplasia, 17; severe dysplasia, 6) with follow-up from 5 to 18 months. Complete regression was seen in 2/14 (14%) patients treated with concentrations of 0.05%----0.1167% and in 10/22 (45%) patients treated with concentrations of 0.1583%----0.484% (p less than 0.05). One patient with negative biopsies at 12 months has subsequently recurred at 18 months.

Administration, Topical↗
PubMed1986

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia.

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-trans-retinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-3H acid (3H-TRA, 500 mu Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.

Administration, Topical↗
PubMed1986

An effective five-drug antiemetic combination for prevention of chemotherapy-related nausea and vomiting. Experience in eighty-four patients.

Antiemetics of known efficacy have been shown to block mainly one of three neurotransmitter receptors in the brain. A combination of antiemetics, designed specifically for outpatient use and consisting of metoclopramide, thiethylperazine, diphenhydramine, dexamethasone, and diazepam, is capable of blocking multiple sites in the emesis pathway. Eighty-four patients receiving highly emetic chemotherapy (85% received cisplatin) completed 200 trials of this five-drug combination using two similar regimens. Complete control (i.e., no nausea or vomiting) was achieved in 45% and two or fewer episodes of vomiting was experienced in 72% of these 200 trials. The mean number of vomiting episodes was 1.65, the median 1.0, and the range 0-15. Sedation was nearly universal, although no serious toxicity was encountered. Thus, this antiemetic combination designed for outpatient use proved highly effective in controlling nausea and vomiting associated with highly emetic anticancer treatment.

Adolescent↗
PubMed1985

Adenylate cyclase in human ovarian cancers: sensitivity to gonadotropins and nonhormonal activators.

Adenylate cyclase activity in particulate preparations of ovarian tumors from 47 women was determined by measuring the conversion of phosphorus 32-labeled adenosine triphosphate to phosphorus 32-labeled cyclic adenosine monophosphate. Ovarian cancers typically exhibited an active adenylate cyclase which was stimulated by 50 mumol/L 5'-guanylylimidodiphosphate and 10 mmol/L of sodium fluoride. This activity was comparable to that in particulates of normal postmenopausal ovaries and was independent of the class of tumor. There was no significant increase in adenylate cyclase activity in any epithelial or germinal tumor in the presence of either 250 nmol/L of human chorionic gonadotropin or 333 nmol/L human follicle-stimulating hormone. However, cyclic adenosine monophosphate production by two sex cord stromal tumors was stimulated by follicle-stimulating hormone, but not by human chorionic gonadotropin. Follicle-stimulating hormone stimulated a threefold increase in activity in the granulosa-theca cell tumor, with an activation constant (57 nmol/L) similar to that in follicle-stimulating hormone-responsive rat ovaries. Prostaglandin E1 (50 mumol/L) increased cyclic adenosine monophosphate production by epithelial tumors more than twofold. These data suggest that sex cord stromal tumors, unlike the more common epithelial tumors, can be modulated directly by gonadotropin.

Adenylyl Cyclases↗
PubMed1984

Sex assignment in gestational trophoblastic neoplasia.

A retrospective survey was performed in 205 cases of gestational trophoblastic neoplasia with the use of routine tissue sections and quinacrine stain after hydrolysis and pronase pretreatment. The method allows scoring of nuclei simultaneously for either Y chromatin or X chromatin (Barr body) and has proved to be a valid test for sex assignment in tissue sections. Y-chromatin positivity (indicating gamete heterozygosity) was found in 16 of 182 cases (9%) of hydatidiform mole, two of four cases (50%) of invasive mole, and 14 of 19 cases (74%) of choriocarcinoma. The cytogenetic literature of 173 cases of complete hydatidiform mole indicates 8.1% have been 46,XY. Our unexpectedly high incidence of Y chromatin in malignant gestational trophoblastic neoplasia would suggest that homozygosity for a recessive mutant oncogene is not an important factor in pathogenesis of choriocarcinoma. The partial allograft theory of pathogenesis after nonmolar antecedents with attendant diminished host immunoreactivity remains a plausible consideration.

Choriocarcinoma↗
PubMed1984

Comparative in vitro cytotoxicity of cyclophosphamide, its major active metabolites and the new oxazaphosphorine ASTA Z 7557 (INN mafosfamide).

Cyclophosphamide (CPA), the most commonly used alkylating agent in the treatment of a wide variety of hematologic and solid tumors, requires oxidation by hepatic microsomal enzymes to its active alkylating species. A number of alternative methods exist to simulate the in vitro cytotoxicity of CPA against animal and human tumors, including the co-incubation of CPA with the S-9 fraction of rat liver homogenates (S-9) and the use of either 4-hydroperoxy CPA (a stabilized form of a major blood-borne metabolite of CPA), phosphoramide mustard (PM, considered to be the ultimate intracellular alkylating metabolite of CPA), or ASTA Z 7557 [4-(2-sulfonatoethylthio)-CPA, a new oxazaphosphorine compound which after dissolution undergoes rapid spontaneous hydrolysis in vitro with liberation of 4-hydroxy-CPA]. Using a human tumor clonogenic assay (HTCA) we have quantitated the median molar inhibitory dose 50 (ID50) concentrations of S-9 activated-CPA, 4-hydroperoxy-CPA, PM, and ASTA Z 7557 against 107 previously untreated tumors, as well as determining the in vitro biological stability of the former three CPA metabolite preparations. 4-Hydroperoxy-CPA proved the most consistently cytotoxic (median molar ID50 = 5.7 X 10(-5)M) compound, followed by ASTA Z 7557, S-9 activated-CPA and PM in that order. Of additional interest S-9 activated CPA and PM proved relatively unstable biologically when frozen at -120 degrees C, whereas 4-hydroperoxy-CPA lost none of its cytotoxicity over a 36 day period during freezing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗