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Biomedical subjects

E A Surwit

Publications and source records attributed to E A Surwit.

At least 73 records · Page 4Linked to original sources
PubMed1984

Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide.

Nausea and vomiting remain common and debilitating side effects of therapy with many anticancer drugs. Recent reports have shown that both metoclopramide and dexamethasone are effective drugs for the treatment of severe nausea and vomiting caused by cis-platinum. A double-blind crossover study comparing the antiemetic properties of high-dose oral and intravenous regimens of metoclopramide and dexamethasone in outpatients was carried out. Standardized patient questionnaires and interviews were used to evaluate response. Dexamethasone and metoclopramide protected against more than five episodes of emesis in 48% and 40% of patients, respectively. Nausea persisted for less than six hours in 45% of patients on dexamethasone and in 37% on metoclopramide. The antiemetic efficacy of both regimens was retained through repeated courses of chemotherapy. Side effects were minimal with dexamethasone; however, 33% of patients experienced unacceptable extrapyramidal side effects to metoclopramide. Patient preference was significantly in favor of dexamethasone: 70% of patients chose to continue dexamethasone compared to 22% who preferred metoclopramide and 8% who chose other antiemetics. Dexamethasone was the preferred antiemetic in this patient population due to minimal side effects.

Adult↗
PubMed1984

Investigation of binding sites for follicle-stimulating hormone and chorionic gonadotropin in human ovarian cancers.

The binding of FSH and hCG to ovarian tumor biopsies from 31 women was analyzed to determine whether ovarian cancers contain receptors for gonadotropic hormones. For comparative purposes, gonadotropin binding to receptor-positive control tissues was also assessed. Specific binding was defined as [125I]hFSH and [125I]hCG binding prevented by coincubation of tissue samples with an excess of unlabeled gonadotropin. Various types of epithelium-derived tumors (serous, mucinous, endometrioid, and undifferentiated; n = 29) had low levels of specific FSH and hCG binding (less than 15% of receptor-positive control tissues) which were not dependent on tissue concentration and not saturable. A germ cell tumor had similar binding characteristics. In contrast, specific FSH binding to a granulosa cell-theca cell (GC-TC) tumor was directly proportional to tissue concentration, and binding was maximal in the presence of 100 ng/ml [125I]FSH. Scatchard analyses of FSH binding yielded a linear plot. Although the FSH-binding capacity of the GC-TC tumor (6.3 fmol/mg) exceeded that of control tissues, their binding affinities (Kd = 1.4 X 10(-9)M) were similar. Specific hCG binding to the GC-TC tumor was low and not dependent on tissue concentration. We conclude that the specific binding of FSH to the GC-TC tumor was characteristic of the interaction of gonadotropin with receptors in target tissues. However, the low level of FSH and hCG binding to tumors of epithelial origin did not represent gonadotropin-receptor binding. Thus, the common ovarian tumors of epithelial origin may not respond directly to gonadotropin, but malignancies of sex cord-stromal origin, such as GC-TC tumors, could be modulated by FSH.

Animals↗
PubMed1984

Poor-prognosis gestational trophoblastic disease: an update.

Ten patients with poor-prognosis gestational trophoblastic neoplasia were treated from 1979 to 1983 primarily with the modified Bagshawe chemotherapy regimen. Four patients were noted to have brain metastases, and one patient had liver metastases. In addition, etoposide (VP-16) was used in seven patients, bleomycin in six, cisplatin in five, 5-fluorouracil in two, and cis-retinoic acid in four patients. Thoracotomy, hysterectomy, and splenectomy were performed after chemotherapy was initiated for isolated resistant disease. At present, nine of the ten patients (90%) are in complete remission for four to 44 months. Significant myelosuppression was encountered in seven patients and life-threatening toxicity was noted in two patients. Currently, poor-prognosis patients are treated with the modified Bagshawe regimen, alternating every other week with etoposide, bleomycin, and cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Immediate termination of intractable vomiting induced by cisplatin combination chemotherapy using an intensive five-drug antiemetic regimen.

A five-drug parenteral antiemetic regimen was administered to 17 patients experiencing intractable vomiting following treatment with cisplatin-containing combination chemotherapy. The five-drug treatment consisted of metoclopramide (1 mg/kg iv), diphenhydramine (50 mg im), dexamethasone (20 mg iv), diazepam (5 mg iv), and thiethylperazine (10 mg im), given together at the initiation of the regimen and repeated on a predefined schedule. The number of emetic episodes, duration of nausea and vomiting, and adverse effects were recorded by trained observers. In addition, all patients completed standardized evaluation forms on the day after treatment. Thirteen patients (76%) remained free of vomiting and three (18%) had only one emesis after beginning the study treatment. No serious toxicity was encountered. We conclude that intractable vomiting induced by cisplatin-based combination chemotherapy can be successfully terminated with an aggressive parenteral antiemetic regimen.

Antiemetics↗
PubMed1983

Multiagent chemotherapy in relapsing ovarian cancer.

A multiagent regimen (vinblastine, bleomycin, hexamethylmelamine, and cis-platinum) partly designed on the basis of data from a human tumor stem cell assay was used to treat 36 patients with relapsing epithelial ovarian cancer. All patients included in this study had previously received alkylating agent therapy, and 78% (28/36) had also received Adriamycin. Thirty-five patients were clinically evaluable for response; eight achieved complete clinical remission, and nine achieved partial remission, for an overall response rate of 49%. The median duration of response was 10 months, and three of the complete responders are in remission at 10+, 17+, and 22+ months. Mild to moderate peripheral neuropathy was the major side effect, occurring in 11% (4/35) of patients. Myelotoxicity was well tolerated. We conclude that this four-drug regimen is effective in the treatment of relapsing ovarian cancer patients and should be considered for study as a front-line combination chemotherapy for previously untreated patients.

Altretamine↗
PubMed1983

Characterization of a new human endometrial carcinoma (RL95-2) established in tissue culture.

A new human endometrial cell line, RL95-2, derived from a Grade 2 moderately differentiated adenosquamous carcinoma of the endometrium has been passaged successfully in cell culture for more than 2 yr. The cells are characteristically epithelioid with well-defined junctional complexes, tonofilaments, filopodialike extensions, and surface microvilli. Nuclei are large, irregular, and invaginated frequently with multiple, prominent, lamellar nucleoli. The cells have a log phase doubling time of 22 to 34 h followed by continued growth at a reduced rate with no apparent plateau phase. They exhibit a strong tendency for piling up as well as for the formation of glandlike dome structures. Karyotypically the line is trisomic 8 (47,XX,+8) and has an 8% frequency of polyploidization. Both cytoplasmic and nuclear estrogen receptors are present. Antihuman alpha-keratin characterizes the cell line as epithelial, nonstromal. The RL95-2 cell line may provide a useful in vitro system for the investigation of the endocrine regulation of endometrial neoplasia.

Adenocarcinoma↗
PubMed1983

Treatment of advanced cancer of the cervix with transperineal interstitial irradiation.

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB, 15 Stage IIIB, 1 Stage IVA) received one (12) or two (9) implants following 40-45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only 1 in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.

Adult↗
PubMed1983

A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia.

A phase I trial was conducted of the vitamin A derivative beta-all-trans-retinoic acid (vitamin A acid; TRA), delivered via a collagen sponge and cervical cap for mild or moderate intraepithelial cervical neoplasia. On the basis of known skin and mucosal membrane toxicity, a concentration of 0.05% TRA in a cream-based vehicle was selected as the starting dose and was escalated later with the use of a modified Fibonacchi scale. The delivery device and the TRA were changed daily for 4 days, and side effects were assessed on days 1, 2, 3, 4, 8, and 30 by clinical and colposcopic examination. Vaginal, cervical, and systemic toxicity were evaluated in 35 patients. No dose-related systemic effects were found; mild cervical inflammation increased in many patients at higher doses. Unacceptably high vaginal toxicity was reached at a TRA concentration of 0.484%. A concentration of 0.372% TRA is recommended for use in phase II trials in mild and moderate cervical intraepithelial neoplasia.

Biopsy↗
PubMed1982

Evaluation of topically applied trans-retinoic acid in the treatment of cervical intraepithelial lesions.

The prevention and/or suppression of preneoplastic foci in animals has been convincingly demonstrated with the use of a variety of compounds, including retinoids. We report here a phase I/II trial of beta-trans-retinoic acid delivered via a collagen sponge/diaphragm insert for neoplasia of the cervix. Eighteen patients with biopsy-proved grades 2 and 3 cervical intraepithelial neoplasia underwent four consecutive daily applications of trans-retinoic aicd to the cervix. Conization of the cervix was performed 4 weeks later. Significant vaginal toxicity in 10 of 18 (55%) patients was unrelated to the concentration or carrying media of the drug. A reduction in size of the intraepithelial lesion was noted by colposcopy in six of 18 (33%) patients with complete resolution of disease at conization in two patients. A new delivery system designed to avoid vaginal toxicity while defining the optimal concentration and dosing schedule for these patients is currently under investigation.

Administration, Topical↗
PubMed1982

In vitro retinoid binding and release from a collagen sponge material in a simulated intravaginal environment.

Four in vitro preparations were constructed to simulate the intravaginal release of two retinoids, all-trans-retinoic acid (t-RA) and 13-cis-retinoic acid (c-RA), from a 0.7% collagen sponge diaphragm insert. Four t-RA concentrations, 0.019, 0.05, 0.1, and 0.15% in methanol were added to the sponge. The release into an artificial vaginal fluid was monitored serially over 72 h by serial analysis for t-RA and c-RA using high-pressure liquid chromatography. In each preparation, retinoid release was immediate and noncontinuous. At 37 degrees C, the retinoids were stable for at least 48 h. Trans-retinoic acid was the predominant retinoid recovered. Only trace amounts of the cis-isomer were released. Peak t-RA levels were 20 microM after 0.01%, 60-80 microM after 0.05%, 100-200 microM after 0.1%, and 320 microM after 0.15%. When the vaginal fluid bath was changed after 5 h, no further significant retinoid release occurred. There was significant loss of up to 70% of the applied t-RA into the collagen sponge. The retinoid binding was concentration dependent (higher binding with higher concentrations) and was maximal only after 24 h of co-incubation. The discontinuous release of t-RA and the high degree of binding to collagen would seem to preclude use of the diaphragm insert as a vaginal drug delivery system, at least for retinoids.

Biocompatible Materials↗
PubMed1982

Activity of isotretinoin against squamous cell cancers and preneoplastic lesions.

We investigated the effect of the synthetic vitamin A derivative isotretinoin (13-cis-retinoic acid) on advanced cancers in 103 patients and on preneoplastic lesions in five patients. Six of 14 patients with squamous cell epithelial cancers had objective regressions of skin or subcutaneous metastases. Three of five patients with preneoplastic lesions had objective responses. The major dose-limiting toxic effects were reversible dermatitis, emotional lability, and headaches. We conclude that the growth of some squamous cell epithelial malignancies can be inhibited by isotretinoin and suggest that other retinoids should be evaluated as antitumor agents.

Antineoplastic Agents↗
PubMed1981

Pharmacologic studies of anticancer drugs with the human tumor stem cell assay.

To optimize the human tumor stem cell assay (HTSCA) for clinical and research purposes we have carried out in vitro pharmacology studies. Useful observations were made in four areas. (1) Drug assay design: The predictive accuracy of the HTSCA depends on the in vitro testing of drug concentrations of less than 10% of those which are pharmacologically achievable with standard in vivo drug doses. The use of unrealistically high in vitro concentrations can accurately predict clinical drug resistance, but is likely to yield high false-positive rates of clinical response prediction. (2) Drug scheduling: For certain schedule-dependent drugs, as well as those with a prolonged plasma half-life and those used according to a repeated daily schedule, prolonged in vitro exposure (rather than 1 h) may be needed to provide an adequate in vitro design. For an accurate prediction of sensitivity of tumor colony-forming units (TCFUs) to continuous drug contact in the agar, concentrations should be in the range of 1/300 that used for the standard 1-h exposure prior to plating. (3) Drug combinations: In preliminary studies of combination chemotherapy in vitro we commonly observed at least additive effects with low doses of cis-platinum plus either vinblastine or adriamycin. (4) Drug bioactivation: Rat liver microsomes or S-9 fraction were used to activate cyclophosphamide for in vitro effect, and satisfactory dose-response curves were observed for the inhibition of TCFUs. Such pharmacologic studies will be required for a wide variety of standard and new agents and will probably become a regular aspect of investigation of new anticancer drugs.

Antineoplastic Agents↗
PubMed1981

Chemotherapy of ovarian cancer directed by the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) has been used to study the in vitro sensitivity rates of anticancer drugs used in the treatment of 115 patients with previously untreated and relapsing ovarian cancer. The data from these studies have identified patterns of cross resistance and residual sensitivity between these agents, and have allowed the prospective selection of single agents possessing in vitro activity for the treatment of 32 patients with relapsing disease. cis-Platinum and vinblastine were the most active agents in vitro against ovarian TCFUs from both previously untreated and relapsing patients. Prior therapy with even one drug was associated with the acquisition of resistance to several classes of compounds (e.g., melphalan resistance was almost always associated with in vitro adriamycin resistance, P less than 0.001). A clinical trial yielding similar data would have required nearly 450 evaluable ovarian cancer patients. In 11 of 32 patients in vitro testing predicted sensitivity to single agents: eight of these had partial remissions for a predictive accuracy of 73%. In 33 instances the HTSCA had 100% accuracy in predicting the lack of clinical response. Thus, the HTSCA for advanced ovarian cancer appears to have a similar predictive accuracy rate to the estrogen receptor assay for predicting the response to hormonal therapy for disseminated breast cancer.

Antineoplastic Agents↗