Biomedical subjects

G P Sutton

Publications and source records attributed to G P Sutton.

At least 37 records · Page 2Linked to original sources

PubMed1994

Phase II study of ifosfamide and mesna in refractory adenocarcinoma of the endometrium. A Gynecologic Oncology Group study.

BACKGROUND: Ifosfamide has antitumor activity in previously treated ovarian epithelial tumors, squamous carcinomas of the cervix, trophoblastic disease, and untreated uterine sarcomas in Gynecologic Oncology Group (GOG) trials. Because cyclophosphamide and other alkylating agents are known to produce responses in adenocarcinoma of the endometrium, a Phase II trial of ifosfamide and the uroprotector, mesna, was undertaken. METHODS: Fifty-two patients with advanced adenocarcinoma of the endometrium recurrent after surgery and/or radiation therapy and refractory to first-line chemotherapeutic agents were treated with ifosfamide, 1.2 g/m2 intravenous daily for 5 days every 4 weeks, and mesna, 300 mg/m2 intravenous every 4 hours for 3 doses daily for 5 days. Two patients were ineligible--one due to prior therapy and one due to a second malignancy. Three patients had an inadequate trial, and 7 were inevaluable for response, leaving 47 patients evaluable for toxicity and 40 patients evaluable for response. Thirty-seven patients had undergone hysterectomy, 30 had received radiation therapy, and 32 had received prior cisplatin-based chemotherapy. All patients were GOG performance status 0, 1, or 2. RESULTS: Complete responses were observed in three (7.5%) and partial responses in three patients (7.5%), for a response rate of 15% (95% confidence interval for the true response rate was 5.5%-29.8%). Severe (Grade 3 or 4) leukopenia and anemia were seen in 25 and 4 patients, respectively. Severe thrombocytopenia was observed in 7 patients. Five patients had Grade 3 or 4 neurotoxicity, and one had Grade 3 renal impairment. Reversible alopecia was universal. CONCLUSIONS: This dose and schedule of ifosfamide and mesna is active in patients with adenocarcinoma of the endometrium failing platinum-based therapy. Phase II testing in untreated patients is under way.

Adenocarcinoma↗

PubMed1994

Phase II trial of menogaril in patients with squamous carcinoma of the cervix: a Gynecologic Oncology Group study.

A phase II trial of 200 mg/m2 menogaril was conducted by the Gynecologic Oncology Group (GOG) in women with advanced or recurrent squamous carcinoma of the cervix who had received no previous chemotherapy. Twenty-three patients were placed on the study; 22 are evaluable for toxicity and for response. One patient had incomplete data and was inevaluable. Nine patients (40.9%) had previously undergone surgery, and 21 (95.5%) had received radiotherapy before this trial. GOG grade 3 granulocytopenia occurred in 1 patient (4.5%) but none developed grade 3 or 4 thrombocytopenia. One patient (4.5%) had grade 3 gastrointestinal toxicity. Neither complete nor partial responses were observed in this trial, although 9 patients (40.9%) had stable disease lasting 2 months or more. Menogaril at this dose and schedule is inactive in advanced or recurrent squamous carcinoma of the cervix.

Adult↗

PubMed1994

A phase II trial of ifosfamide and mesna in patients with advanced or recurrent mixed mesodermal tumors of the ovary previously treated with platinum-based chemotherapy: a Gynecologic Oncology Group study.

A phase II trial of ifosfamide and mesna in women with mixed mesodermal tumors of the ovary who had previously received platinum-containing chemotherapy was conducted by the Gynecologic Oncology Group (GOG). The starting dose of ifosfamide was 1.2 g/m2 daily iv for 5 days. Mesna was given intravenously with and at 4 and 8 hr following the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. Thirty-two patients were placed on the study; 31 were evaluable for toxicity and 28 for response. Twenty-seven patients (87.1%) had previously undergone surgery and three (9.3%) had received radiotherapy before this trial. GOG grade 3 or 4 granulocytopenia occurred in 11 (35.5%) patients, and one (3.2%) developed grade 4 thrombocytopenia. Two patients (6.4%) had grade 3 neurotoxicity. A complete response was observed in one patient (3.6%) and partial responses in four patients (14.3%) for a total response rate of 17.9% (95% confidence interval = 6.1-36.9%). In conclusion, ifosfamide has activity in previously mixed mesodermal tumors of the ovary.

Adult↗

PubMed1994

Epithelial ovarian cancer complicating renal transplantation.

Patients taking immunosuppressive therapy are at substantial risk for malignant disease. We report two cases of epithelial ovarian cancer occurring in women after renal transplantation with subsequent poor clinical outcome. Clinicians are advised to thoroughly investigate adnexal masses in this patient population.

Adult↗

PubMed1994

Secondary therapy for epithelial ovarian cancer--1994.

In women with recurrent epithelial ovarian cancer, secondary treatment options include surgery and chemotherapy. Surgery should be considered in patients with persistent disease at the time of second-look laparotomy and before chemotherapy in those whose disease recurs following long-term remission. With regard to secondary chemotherapy, active agents include cisplatin, carboplatin, ifosfamide, and paclitaxel. The effectiveness of hexamethylmelamine as salvage therapy is less clear, although it may be of use in patients who relapse soon after receiving primary platinum chemotherapy. Patients who receive platinum therapy initially and relapse after long periods of remission often respond to second-line platinum treatment. Ifosfamide may be effective in patients receiving one or two prior cisplatin-containing regimens, but is contraindicated in those with hepatic or renal insufficiency. Paclitaxel is the drug of choice for patients who have developed primary resistance to platinum therapy.

Antineoplastic Agents↗

PubMed1994

Chyloperitoneum following treatment for advanced gynecologic malignancies.

BACKGROUND: Chyloperitoneum is an uncommon complication following retroperitoneal surgery. Blunt abdominal trauma, abdominal surgery, abdominal or pelvic radiation, cirrhosis, lymphoma, tuberculosis, and congenital defects of lacteal formation may also lead to chylous ascites. CASES: Two patients developed chylous ascites after treatment for gynecologic malignancies. One, who also received pelvic and abdominal radiation, developed chylous ascites 11 months after retroperitoneal lymph node dissection for advanced endometrial cancer. She was treated with a diet low in fat and high in medium-chain triglycerides, as well as with intravenous hyperalimentation. She had recurrences of chylous ascites, which responded to paracentesis and intravenous hyperalimentation. The second patient developed chylous ascites 2 months after retroperitoneal lymph node dissection for advanced fallopian tube cancer. She was treated with a medium-chain triglyceride diet, which resulted in resolution of her symptoms. CONCLUSION: Chyloperitoneum is an uncommon complication following treatment for gynecologic malignancies. Our second case is the first reported in which retroperitoneal lymph node dissection for gynecologic malignancy resulted in chyloperitoneum. However, because gynecologic malignancies frequently metastasize to the periaortic lymph nodes, chylous ascites may be an important cause of morbidity following treatment.

Adenocarcinoma↗

PubMed1994

Growing teratoma syndrome after chemotherapy for germ cell tumors of the ovary.

BACKGROUND: The growing teratoma syndrome has been described with regard to gonadal and extragonadal germ cell neoplasms in males, but few cases have been reported in the female population. In this condition, masses that enlarge during or after chemotherapy are found to contain mature teratoma without malignant elements. CASES: Three patients had either persistent or growing masses despite chemotherapy for germ cell malignancies of the ovary. All cases fit the description of the growing teratoma syndrome. The patients were aged 20-22 years. All three patients had immature teratomas before chemotherapy. The stages of disease ranged from Ia to IIIc. All patients had normal tumor markers while their masses showed growth or persistence. All were free of disease 6-31 months after diagnosis. CONCLUSION: Growth or persistence of a tumor after chemotherapy for malignant teratoma does not necessarily imply progression of malignancy, especially if tumor markers are normal. However, these masses should be resected because they may cause obstruction, compression, or displacement of adjacent organs, or undergo sarcomatous degeneration.

Adult↗

PubMed1993

Vulvar melanoma reconsidered.

BACKGROUND: Melanoma of the vulva has traditionally been treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy. Cutaneous nonvulvar melanoma has been successfully treated with local excision with selective therapeutic regional node dissection. METHODS: A retrospective analysis of 16 patients with primary malignant melanoma of the vulva who underwent surgery from 1973 to 1988 at Indiana University Hospital was conducted. The purpose of this analysis was to determine if less radical surgery, such as that performed for cutaneous nonvulvar melanoma, might be adopted for patients with vulvar melanoma without compromising 5-year survival results. RESULTS: Surgical therapy included radical vulvectomy with bilateral inguinofemoral lymphadenectomy (n = 11), radical vulvectomy alone (n = 1), and wide local excision (n = 4). Treated International Federation of Gynecology and Obstetrics (1971) stages included I (n = 12), II (n = 3), and III (n = 1). The median age of the patients was 59 years (range, 29-79 years). The median depth of invasion according to the Breslow method was 3 mm (range, 0.1-8 mm). Patients were observed for a median of 24 months (range, 3-143 months). The Kaplan-Meier 5-year survival estimate was 30%. There were nine recurrences: five distant, one central, one nodal, and two mixed. A median depth of 0.9 mm (range, 0.1-1.75 mm) was noted in those who remained disease-free versus 4.6 mm (range, 3-8 mm) in those who experienced a recurrence (P < 0.01). None of the patients with lesion depths of 1.75 mm or smaller experienced a recurrence, whereas all of those with lesion depths larger than 1.75 mm suffered a recurrence (P = 0.0004). CONCLUSIONS: Patients with lesion depths of 1.75 mm or smaller may be treated with wide local excision. Patients with greater lesion depths are at high risk for the development of distant metastases. The patients with well-lateralized lesions may be equally well served with a less morbid procedure deferring therapeutic node dissection until there is a regional recurrence.

Adult↗

PubMed1993

Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study.

A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced nonsquamous carcinoma of the cervix. A starting dose of 1.5 g/m2 IFX iv daily for 5 days and 300 mg/m2 mesna iv every 4 hr with three doses daily after IFX were given. In patients who had received prior radiotherapy or chemotherapy, the starting dose of IFX was reduced to 1.2 g/m2. Forty-six patients were entered, and 41 are evaluable for toxicity. Forty patients are evaluable for response. Age range was 30-72 yr. GOG performance status was 0-1 for all but 2 patients. Fifteen patients (37.5%) developed GOG grade 3 or 4 granulocytopenia, and 1 developed grade 4 thrombocytopenia. One patient developed transient renal insufficiency. There was one complete response and five partial responses (12.5%) for a response rate of 15.0%. Median response duration was 4.2 months (range, 1.7-22.6 months). Three responses were seen in areas with pelvic disease only. Three responses were observed in extrapelvic sites. IFX possesses activity which compares favorably with that of other agents in this disease.

Adenocarcinoma↗

PubMed1993

Blood transfusion and the risk of recurrence in squamous carcinoma of the vulva.

OBJECTIVE: Our purpose was to determine if postoperative transfusion increases the risk of recurrence in patients who have undergone operation for squamous carcinoma of the vulva. STUDY DESIGN: Data from 154 patients with squamous carcinoma of the vulva treated at Indiana University Medical Center from 1974 through 1988 were retrospectively analyzed to determine the influence of postoperative transfusion on recurrence risk. Patients were evaluated for International Federation of Gynecology and Obstetrics stage, lesion size, lesion depth, grade, patient age, number of transfusions, and recurrence with chi 2 analysis, Fisher's exact test, and the Student t test where appropriate. RESULTS: Transfusions were given to 57 patients (37%) with a mean of 2.2 units delivered (range 1 to 5 units). Transfused patients differed significantly from those not transfused in that they had more advanced stage (p = 0.002), more positive nodes (p = 0.03), and higher grade lesions (p = 0.03), and they were older (p = 0.005). Recurrences developed in 25 patients (16.2%). Recurrences were more common in those with positive nodes (10-39, 25.6%) than in those with negative nodes (8/99, 8%), (p = 0.01). Only nodal status was predictive of recurrence in this series. Transfused patients had a 14% (8/57) rate of recurrence, whereas the recurrence risk was 17.5% (17/97) in those not transfused (p = 0.65). CONCLUSIONS: We have been unable to confirm that postoperative transfusions increase the risk of recurrence in patients with squamous carcinoma of the vulva.

Adult↗

PubMed1993

Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study.

OBJECTIVE: Our objective was to determine the activity of ifosfamide and mesna in women with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy. STUDY DESIGN: This is a phase II drug study in which the starting dose of ifosfamide was 1.5 gm/m2 daily intravenously for 5 days. The starting dose of ifosfamide was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy. The uroprotector mesna was given intravenously with, and at 4 and 8 hours after, the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. RESULTS: Fifty-six patients were placed in the study; 52 were evaluable for toxicity and 51 for response. Twenty-eight (54.9%) patients had previously undergone surgery and 46 (90.2%) had received radiotherapy before this trial. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in 7 (13.5%) patients, and 2 (3.9%) had grade 3 thrombocytopenia. Six (11.5%) patients had grade 3 or 4 neurotoxicity. Complete response was observed in 2 (3.9%) patients and partial responses in 6 (11.5%) patients, for a total response rate of 15.7% (95% confidence interval 7.02% to 28.59%). CONCLUSIONS: This response rate is higher than that reported by the Gynecologic Oncology Group in patients with previously treated squamous carcinoma of the cervix. Our findings fail to confirm that ifosfamide is a highly active agent in patients with squamous carcinoma of the cervix as reported by others; nonetheless, the observed activity of this drug deserves further study in combination therapy of squamous carcinoma of the cervix.

Adult↗

PubMed1992

Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to evaluate the activity of ifosfamide (isophosphamide) in patients with advanced or recurrent leiomyosarcoma not previously exposed to chemotherapy. STUDY DESIGN: This is a phase II groupwide study of the Gynecologic Oncology Group. Thirty-five patients were treated with ifosfamide 1.5 gm/m2 daily intravenously for 5 days with mesna (mercaptoethane sodium sulfonate). Fifty-six patients had received prior abdominal hysterectomy and 15 prior radiotherapy. The dose was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy. RESULTS: Gynecologic Oncology Group grade III or IV granulocytopenia occurred in 4 (11%) patients, and none had grade IV thrombocytopenia. One (2.8%) patient had grade IV neurotoxicity. Partial responses were observed in 6 of 35 (17.2%) patients. The 95% confidence interval for response was 6.6% to 33.7%. CONCLUSION: These results indicate that ifosfamide has modest activity in patients with advanced or recurrent leiomyosarcomas of the uterus.

Adult↗

PubMed1992

Ovarian metastases in stage IB carcinoma of the cervix: a Gynecologic Oncology Group study.

Surgical and pathologic findings at laparotomy for radical hysterectomy in 990 patients with clinical stage IB carcinoma of the cervix were analyzed to determine the frequency of metastases to the ovary. Ovarian spread was identified in 4 of 770 (0.5%) patients with squamous carcinoma and 2 of 121 (1.7%) with adenocarcinoma. No patients with adenosquamous carcinoma (n = 82) or other histologic types (n = 17) had ovarian metastases. Although the frequency of metastases was greater among patients with adenocarcinoma, this was not statistically significant (p = 0.19, Fisher's exact test). All 6 patients with ovarian metastases had other evidence of extracervical disease. Three underwent radical hysterectomy and bilateral salpingo-oophorectomy. Of these, one patient received extended field radiotherapy and died of disease 18 months after diagnosis. Two patients, one treated with combination chemotherapy and one with no adjunctive therapy, are alive without evidence of disease at 59 and 62 months, respectively. Three patients underwent exploratory laparotomy with salpingo-oophorectomy and lymphadenectomy without hysterectomy. All three patients died of disease at 2, 3, and 30 months; the first and last patient received adjunctive radiotherapy. Not all patients underwent oophorectomy. Of 347 patients with at least unilateral ovarian preservation, no postoperative pelvic radiotherapy, and no gross extracervical disease or metastasis to the paraaortic nodes, pelvic recurrence developed in 16. There was no excess of pelvic recurrences in patients with adenocarcinoma (0/41) or adenosquamous carcinoma (1/29, 3.4%) when compared with those with squamous carcinoma (15/270, 5.6%). This suggests no excess of occult ovarian metastases in nonsquamous tumors of the cervix. There is no evidence in these data of an increased risk of ovarian preservation in patients with stage IB carcinoma of the cervix with no gross extracervical disease.

Adenocarcinoma↗

PubMed1992

Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity in extracts of ovarian carcinomas.

Cancer cells have an increased ability to synthesize GTP (guanosine triphosphate) because of increased activity of IMP DH (inosine 5'-phosphate dehydrogenase, EC 1.1.1.205). Because IMP DH activity is rate limiting for de novo biosynthesis of GTP, this enzyme was suggested as a sensitive target for chemotherapy. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) is converted in the cells into the active metabolite, TAD, (thiazole-4-carboxamide adenine dinucleotide) which potently inhibits IMP DH activity. By adding TAD to tissue extracts one can determine the extent of inhibition of IMP DH. We applied the IMP DH assay method to extracts of normal ovaries (N = 11) and epithelial ovarian carcinomas (N = 10). The IMP DH activity (mean +/- SE) in ovarian carcinoma was 21.1 +/- 5.8 which was markedly higher than that observed in normal ovaries (2.9 +/- 0.7 nmol/hr/mg protein) (P < 0.05%). The inhibition by TAD of IMP DH activity in ovarian carcinomas (N = 4) was 81%. The results indicate that IMP DH activity is elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be inhibited by exposure to tiazofurin (TAD). Similar high IMP DH activity and inhibition of the activity by TAD was observed in patients with chronic granulocytic leukemia in blast crisis among whom 70 to 80% remissions were reported. Since there is increased IMP DH activity in human ovarian carcinomas and in OVCAR-5 cells and tiazofurin and TAD inhibit IMP DH activity of these cells and the proliferation of human ovarian carcinoma xenografts in the mouse, tiazofurin may merit serious consideration for a Phase II trial for patients with recurrent/refractory epithelial ovarian carcinoma.

Adenocarcinoma↗

PubMed1992

Ifosfamide alone and in combination in the treatment of refractory malignant gestational trophoblastic disease.

OBJECTIVE: We attempted to evaluate the use of ifosfamide either alone or in combination in patients with refractory malignant gestational trophoblastic disease. STUDY DESIGN: Our study comprised, in part, a phase II multiinstitutional trial of ifosfamide in refractory gynecologic malignancies and, in part, a review of institutional experience with ifosfamide in combination chemotherapy. RESULTS: Single-agent ifosfamide produced a significant response in titer in one of two patients with refractory choriocarcinoma. Ifosfamide with etoposide and cisplatin (also known as VIP) resulted in significant response in human chorionic gonadotropin titers in three patients with highly refractory metastatic gestational trophoblastic disease and one cure in this group of patients. CONCLUSION: Ifosfamide has activity in refractory choriocarcinoma and, when combined with etoposide and cisplatin (VIP), may be curative.

Adolescent↗

PubMed1992

Recurrent squamous carcinoma of the vulva.

OBJECTIVE: This study reviews experience at Indiana University with recurrent squamous carcinoma of the vulva over an 18-year period from 1971 to 1989. The pattern of recurrence, time interval to recurrence, and efficacy of salvage therapy are evaluated in the context of the primary tumor. STUDY DESIGN: This is a retrospective study of 40 patients, 21 of whom underwent primary therapy for invasive squamous carcinoma of the vulva at Indiana University. RESULTS: Vulvar recurrences were observed in 17 patients (43%), the groin was involved in 12 (30%), whereas pelvic and distant recurrences were observed in 2 (5%) and 9 (22.5%) patients, respectively. Salvage surgery and/or radiotherapy were successful in 25 patients (62.5%) alive from 1 to 144 months (median 8 months) from secondary therapy. Survival after retreatment varied significantly by site of recurrence (p = 0.002), tumor grade (p = 0.009), and interval to recurrence (p < 0.001). Best outcomes were in patients with initial stage I or II disease (International Federation of Gynecology and Obstetrics), grade 1 tumors, local failure, and interval to relapse of > 16 months' duration. Two of 12 patients with groin recurrences were salvaged with surgery and radiotherapy. CONCLUSION: Long-term follow-up of patients with vulvar cancer and careful restaging at the time of recurrence are mandatory. Although local and nodal recurrences may be controlled with surgery and/or radiotherapy, regional recurrences are usually fatal.

Adult↗

PubMed1992

Epithelioid hemangioendothelioma of the clitoris: a case report with immunohistochemical and ultrastructural findings.

A 30-year-old woman was referred for evaluation of a small nodule of the clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma. This rare vascular tumor of intermediate malignancy has not been previously described in the vulva. The patient underwent a modified radical vulvectomy and bilateral inguinal lymph node dissection, and subsequently received photon therapy. She is alive with no evidence of disease 27 months after diagnosis.

Adult↗

PubMed1992

Flow cytometric DNA analysis of placental-site trophoblastic tumors.

The placental-site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia. Although originally considered benign, it is now apparent that this lesion can be associated with aggressive clinical behavior. Our study examined the DNA ploidy status and clinicopathologic features of four new cases of placental-site trophoblastic tumor. Three cases demonstrated diploid DNA stemlines with S-phase fractions ranging from 6% to 16%. These patients were alive and well at follow-up and had low-serum human chorionic gonadotrophin (hCG) levels. A fourth patient, who had a large tumor, demonstrated a tetraploid DNA peak with a prominent S-phase fraction. This patient exhibited an elevated serum hCG at limited follow-up. Flow cytometric DNA analysis may be a useful adjunct for the identification of placental-site trophoblastic tumors with malignant potential.

Adult↗