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G P Sutton

Publications and source records attributed to G P Sutton.

At least 55 records · Page 3Linked to original sources

Immunohistochemical study of HER-2/neu, epidermal growth factor receptor, and steroid receptor expression in normal and malignant endometrium.

HER-2/neu oncogene protein, epidermal growth factor receptor, progesterone receptor, and estrogen receptor were examined immunohistochemically in specimens of normal and neoplastic endometrium. Tissues obtained at the time of hysterectomy were snap-frozen at liquid nitrogen temperature and serially sectioned at 4 microns. Normal endometrial epithelial cells stained with anti-epidermal growth factor receptor and anti-HER-2/neu with intensities graded from 0 to 3+. Of the 49 endometrial malignancies studied, seven (14%) contained tissue exhibiting HER-2/neu staining in excess (4+) of any of the normal tissues or the other 42 cancer specimens. Expression of both HER-2/neu and steroid receptors was heterogeneous within these seven tumors. To examine this heterogeneity more closely, sections of these and other tumors were double-stained for HER-2/neu and progesterone receptor. It was found that the cells exhibiting 4+ HER-2/neu staining were progesterone receptor-negative. Conversely, cells that were progesterone receptor-positive within the same specimen exhibited HER-2/neu immunostaining equal to or less than 3+. All specimens containing 4+ HER-2/neu tissue were graded 1 or 2 adenocarcinomas, stage I. Thus, there is an inverse relationship between overexpression of HER-2/neu and progesterone receptor in endometrial cancer. On the other hand, overexpression of HER-2/neu in endometrial cancer does not seem to be related to loss of other differentiated characteristics. The prognostic value of these observations awaits continued study.

Biomarkers, Tumor↗

Gynecologic Oncology Group studies with ifosfamide.

The Gynecologic Oncology Group has conducted a series of phase II studies with ifosfamide and mesna since 1985. Previously untreated patients received ifosfamide 1.5 g/m2 intravenously daily for 5 days. Mesna was given intravenously every 4 hours three times daily at 20% of the daily ifosfamide dose. Because of the toxic effects observed in previously treated patients with ovarian cancer, the ifosfamide dose was reduced to 1.2 g/m2/d in patients with prior chemotherapy or radiotherapy. In epithelial ovarian cancer, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses. In patients with squamous carcinoma of the cervix, an 11.1% response rate (three of 27 patients) was observed in those who had received prior platinum therapy. In 51 previously untreated patients, the response rate was 15.7%. In nonsquamous cervical carcinomas, there were three partial responses among 25 patients (12%). An 8.6% response rate was observed among 23 patients with previously treated endometrial adenocarcinomas. In uterine sarcomas, response rates were 30.7% in mixed müllerian tumors, 17.2% in leiomyosarcomas, and 27.3% in endometrial stromal sarcomas. Patients with ovarian sarcomas responded in 27.8% of cases. Studies with ifosfamide combinations are currently under way by the Gynecologic Oncology Group.

Adenocarcinoma↗

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Adult↗

Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988.

From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced.

Adult↗

Stage III ovarian tumors of low malignant potential treated with cisplatin combination therapy (a Gynecologic Oncology Group study).

By serendipity we have had the opportunity to evaluate cis-platin-based chemotherapy in ovarian tumors of low malignant potential (LMP). Optimal (less than 1 cm residual disease) FIGO stage III ovarian carcinomas were randomly assigned to treatment with cisplatin plus cyclophosphamide with or without doxorubicin on a prospective Gynecologic Oncology Group Study. On review by the Gynecologic Oncology Group Pathology Committee, 32 of these cases were determined to represent low malignant potential tumors. Mean age of patients with these lesions was 48 years (range, 25-75 years). After initial cytoreduction, 19 patients had residual disease less than 1 cm and 13 had no residual. Twenty (62.5%) received cisplatin plus cyclophosphamide and 12 cisplatin, cyclophosphamide, and doxorubicin chemotherapy; 75% of patients received six or more courses. Second-look surgery was done in 15 cases; only six were negative. However, with a median follow-up of 31.7 months (range, 1-75), only 1 patient has died; no cancer was found at autopsy. The remaining patients are alive without clinical evidence of disease at a median of 30 months. The need for adjunctive therapy in patients with advanced LMP tumors remains speculative.

Adult↗

Analysis of invasive squamous cell carcinoma of the vulva and vulvar intraepithelial neoplasia for the presence of human papillomavirus DNA.

We have analyzed a number of invasive squamous cell carcinomas for the presence of human papillomavirus (HPV) DNA using dot blot and Southern blot analysis. Seven of 31 samples (23%) were positive by dot blot and/or Southern blot analysis. In contrast, six of 11 (55%) of vulvar intraepithelial neoplasias contained HPV DNA by dot blot and/or Southern blot hybridization. Less than 50% of the invasive vulvar carcinomas contained detectable HPV DNA. The average age at onset of vulvar carcinoma is higher than that for cervical carcinoma (in which HPV DNA is detected in over 80% of cases). Therefore, the role of HPV in the genesis of vulvar carcinoma may be different from the role of HPV in the genesis of cervical carcinoma.

Adult↗

Phase II trial of vinblastine in advanced ovarian carcinoma. A Gynecologic Oncology Group study.

A phase II trial of vinblastine in patients with refractory epithelial ovarian adenocarcinoma of the ovary was conducted by the Gynecologic Oncology Group (GOG) between March 9, 1988 and July 7, 1988. Vinblastine was administered in a dose of 9 mg/m2 intravenously every three weeks until disease progression or toxicity supervened. Twenty patients were entered initially. One was ineligible due to a previous primary cancer. Thus, 19 patients are evaluable for toxicity and response. All patients had cisplatin-combination chemotherapy and four had prior radiotherapy. Median age was 63 years (range 40-75 years). Thirteen patients had disease in the pelvis and six had extrapelvic metastases. Ten patients had grade 3 lesions and seven had grade 2. A median of two courses (range: 1-6) were administered. Toxicity was moderate. Seven patients (36.8%) experienced GOG grade 3 or 4 leukocytopenia and six had grade 3 or 4 granulocytopenia. Median nadir WBC was 2,000 cells/microliters (range 600-3,500) and platelet nadirs for the three patients with thrombocytopenia were 60,000, 116,000, and 147,000. Other toxicity included grade 3 gastrointestinal and renal toxicity in one patient each. Seven patients (36.8%) had stable disease on therapy and 12 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in patients with resistant epithelial ovarian adenocarcinoma progressing on first-line chemotherapy.

Adenocarcinoma↗

Early phase II Gynecologic Oncology Group experience with ifosfamide/mesna in gynecologic malignancies.

Starting in July 1985, the Gynecologic Oncology Group conducted a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received 1.5 g/m2 i.v. ifosfamide daily for 5 days. Mesna was given i.v. q4h x 3 following ifosfamide; each dose was 20% of the daily ifosfamide dose. All patients with ovarian and 87% of those with cervical cancer had previously undergone platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2 daily in all patients who had received prior chemo- or radiotherapy. In epithelial ovarian carcinoma, responses were observed in 8 (20.0%) of 41 evaluable patients, with 3 (7.0%) complete responses. Response duration was 2.1-20.3+ months, with a median of 6.9+ months. In squamous-cell carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients showed partial responses of 1.8, 2.2, and 3.1 months' duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) achieved complete and 3 (11.5%) showed partial responses, for an overall response rate of 30.7%. Response duration was 1.4(+)-8.6 months, with a median of 3.8 months. Toxicity included two deaths due to renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Agents↗

Phase II study of vinblastine in previously treated squamous carcinoma of the cervix. A Gynecologic Oncology Group study.

Thirty-six patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery or first-line chemotherapy were eligible for a phase II study employing vinblastine in a dose of 9 mg/m2 intravenously every 3 weeks until disease progression or toxicity supervened. Two patients were never treated, leaving 34 patients evaluable for toxicity. One patient was inevaluable for response, leaving 33 evaluable for this parameter. Thirty-two patients had prior radiotherapy and 30 had prior chemotherapy. All patients had Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2. Median age was 46 years. Twenty patients had disease in the pelvis and 13 had extrapelvic metastases. Fourteen patients had grade 3 lesions. A median of three courses (range: 1-12 courses) was administered. Ten patients (29.4%) experienced GOG grade 3 or 4 leukocytopenia and 10 had grade 3 or 4 granulocytopenia. Other toxicity included grade 4 gastrointestinal toxicity and anemia in one patient each and two patients with grade 3 neurotoxicity. Twenty patients (60.6%) had stable disease with therapy and 13 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in previously treated patients with squamous carcinoma of the cervix.

Adult↗

Papillary serous carcinoma of the ovary with squamous differentiation.

Two cases of serous carcinoma of the ovary with squamous differentiation are described. These neoplasms occurred in two women who were 63 and 46 years old and who presented with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and III disease, respectively. The first tumor recurred following chemotherapy; radiotherapy was given, but the patient died of tumor at 4 years. The second neoplasm did not respond to chemotherapy and caused the patient's death at 2 years. In the first case, the squamous differentiation occurred as compact nests of ovoid to spindle cells intermixed with a papillary serous carcinoma component. The squamous component of the second case developed as single or small groups of enlarged, eosinophilic cells, often multinucleated, within nests of papillary serous carcinoma with typical psammoma bodies. In the latter case, intercellular bridges were identified by light microscopy. Both cases showed squamous features by immunohistochemistry, staining positively for 57-kd keratin, although in the first case but not the second there was also some weaker staining for 54-kd keratin, probably indicating incomplete squamous differentiation with retained glandular features. Electron microscopy in both cases revealed prominent cytoplasmic tonofilaments in the squamous component. These two cases reinforce the concept that squamous differentiation, although more frequent in some other types of common epithelial tumors, may occur in serous ovarian carcinomas as well.

Carcinoma, Papillary↗

The significance of positive peritoneal cytology in endometrial cancer.

Various studies over the years have demonstrated malignant cells in the peritoneal fluid in the majority of patients with advanced ovarian carcinoma, thereby suggesting that the absence of malignant cells in early ovarian cancer might indicate a favorable prognosis. However, in endometrial adenocarcinoma, the significance of malignant peritoneal cytology has been less well defined. In the author's study of 615 patients, clinical stage, histologic grade, age of patient, and the results of peritoneal cytology correlated with survival. Survival of clinical Stage I patients with negative peritoneal cytology was superior to that of those with malignant cytology. However, proper assessment of peritoneal cytology as an independent risk factor awaits a prospective study, as does the need for or type of therapy for patients with malignant cytology.

Adenocarcinoma↗

Gynecologic Oncology Group experience with ifosfamide.

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Peritoneal cytology in endometrial carcinoma.

The ultimate role played by peritoneal cytologic evaluation in endometrial cancer remains somewhat ill-defined. Proper assessment of peritoneal cytology as an independent risk factor awaits a prospective study in which patients with malignant peritoneal cytology and surgical Stage I lesions are not treated and survival is compared to controls with negative cytology. Such a study is unlikely to be done, given results available from retrospective analyses and the large number of patients needed to complete such a trial. Whether therapy is needed and which type to use in patients with malignant cytology remain uncertain. Half of these patients will presumably require pelvic radiotherapy for adnexal, nodal, or other pelvic spread. Potish et al. have advocated the use of whole-abdominal radiotherapy in such patients, with favorable results. In patients without extrauterine spread, Creasman et al. have championed the postoperative use of intraperitoneal radioactive phosphate. They based their recommendation on survival results in a group of 23 patients with positive washings who were treated with intraperitoneal radioactive chromic phosphate. In this group, the recurrence rate was reduced, when compared to historic controls, to 13% (3/23), all of whom had extra-abdominal recurrences. Soper et al. confirmed the safety of postoperative radioactive chromic phosphate in doses of approximately 15 millicuries in patients with endometrial cancer. In their study of 65 patients, 56 had percutaneous catheter placement under local anesthesia after laparotomy. In one patient, the catheter could not be used because of poor distribution of the technetium Tc 99m sulfur colloid tracer, and in a second subject, fever and peritoneal signs suggesting bowel perforation led to removal of the insertion catheter. No other significant problems were encountered in 48 patients treated with radioactive chromic phosphate without other therapy. In contrast, five of seventeen patients who received external pelvic radiotherapy in addition to radioactive chromic phosphate suffered bowel complications requiring surgical intervention. Two of these patients died of operative complications, suggesting that radioactive chromic phosphate cannot be safely combined with standard dose external radiotherapy. In a retrospective series, Mazurka et al. intimated that adjunctive chemotherapy might be useful in patients with malignant cytology, but such an approach is untested. A prospective randomized study of radioactive chromic phosphate, whole abdomen radiotherapy, or adjunctive chemotherapy versus no treatment in patients with malignant peritoneal cytology is clearly needed.

Ascitic Fluid↗

Phase II study of ifosfamide and mesna in patients with previously-treated carcinoma of the cervix. A Gynecologic Oncology Group study.

Thirty patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery and refractory to first-line chemotherapeutic agents were treated with ifosfamide in a dose of 1.2 grams/m2 IV daily for five days every four weeks and Mesna 300 mg/m2 IV every four hours for three doses daily for five days. One patient had an inadequate trial and two were inevaluable for response, leaving 27 patients evaluable for response. All but two patients had received prior radiotherapy and all but one prior cisplatin-based or cisplatin analog chemotherapy. Seventeen patients had prior surgery. All patients were Gynecologic Oncology Group performance status 0, 1, or 2. Partial responses were observed in three patients (11.1%), two with pelvic and one with extrapelvic disease. A 90% confidence interval for the true response rate is 4.5%-24.8%. Severe (grade 3 or 4) leukopenia and anemia were seen in nine and seven patients, respectively. Severe thrombocytopenia was not observed. Three patients had grade 3 or 4 neurotoxicity, and one had grade 3 renal impairment. Reversible alopecia was universal. This dose and schedule of ifosfamide and Mesna is active in patients with squamous carcinoma of the cervix failing platinum-based therapy. Phase II testing in untreated patients is currently underway.

Adult↗

Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study).

A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.

Adult↗

Features associated with survival and disease-free survival in early endometrial cancer.

Age, clinical stage, histologic grade, depth of myometrial penetration, adnexal status, peritoneal cytology, and progesterone and estrogen receptor status were available for 139 patients with clinical stage IA, IB, or II endometrial adenocarcinoma who had therapy at Indiana University Hospital or St. Vincent Hospital in Indianapolis. These features were analyzed for their association with survival and disease-free survival. Patients treated at Indiana University Hospital were similar to those from St. Vincent Hospital when comparisons were made by chi 2 test for age, clinical stage, grade, adnexal metastases, peritoneal cytologic results, progesterone receptor status, or estrogen receptor status. However, patients treated at Indiana University Hospital had lesions that were deeper (p = 0.03) than those treated at St. Vincent Hospital. Survival differences were observed for patients with progesterone receptor-rich versus progesterone receptor-poor tumors (p = 0.004), grades 1 and 2 versus grade 3 lesions (p = 0.013), and malignant versus benign peritoneal cytologic results (p = 0.01). Differences in disease-free survival were observed for those patients with adnexal metastases versus those with no adnexal disease (p = 0.002), those with estrogen receptor-rich versus estrogen receptor-poor tumors, outer third myometrial invasion (p = 0.002), and patients with clinical stage I versus clinical stage II disease (p = 0.03). A stepwise Cox proportional hazards model was constructed to determine correlates of disease-free survival. In the final model, grade (p = 0.0002), peritoneal cytologic results (p = 0.0002), progesterone receptor status (p = 0.004), and age as a continuous variable (p = 0.008) were most closely associated with disease-free survival.

Adenocarcinoma↗