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H D Homesley

Publications and source records attributed to H D Homesley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Radiation-induced vesicosacral fistula: treatment with continent urinary diversion.

This is the first Case Report of a vesicosacral fistula related to prior radiation therapy. This patient developed recurrent adenosquamous carcinoma of the cervix 1 year after radical hysterectomy. She received 5000 cGy to the whole pelvis and a 1500-cGy boost to the area of recurrence in the right pelvic sidewall. The patient had significant toxicity with recurrent pelvic fistula formation ultimately requiring an end sigmoid colostomy. In addition, the patient required urethral catheterization due to urinary incontinence secondary to a hypertonic bladder. Approximately 14 years after radiation therapy the patient developed a vesicosacral fistula. With a nonfunctional bladder, the decision was made to proceed with a continent urinary diversion procedure. Despite a prior ileocecal resection due to radiation injury, a Miami pouch reservoir was created. Postoperatively, the patient remained continent using intermittent catheterization of the pouch.

Adenocarcinoma↗
PubMed1995

A phase II trial of gallium nitrate (NSC #15200) in nonsquamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

A Phase II trial of gallium nitrate for patients with recurrent or metastatic nonsquamous cell carcinoma of the cervix was conducted by the Gynecologic Oncology Group (GOG) from March 1988 to January 1992. Twenty-six evaluable patients were treated with 750 mg/m2 of gallium nitrate every 3 weeks. Age range was 30-74 years with a median of 48 years. GOG performance status was 0-1 for all but four patients. Two patients had a complete response (7.7%), 1 patient had a partial response (3.8%), 13 patients had stable disease (50.0%), and 10 (38.5%) had increasing disease. The 95% confidence interval for response is 2.4-30.2%. The major toxicities were nausea, vomiting, and anemia. Gallium nitrate has modest activity in patients with nonsquamous cell carcinoma of the cervix.

Adenocarcinoma↗
PubMed1995

Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.

PURPOSE: Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy. PATIENTS AND METHODS: Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles. RESULTS: At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P < .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type. CONCLUSION: This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.

Adult↗
PubMed1995

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

Adult↗
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

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

The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer, in which the maximum diameter of residual is < or = 1 cm, and suboptimal residual cancer, in which the residual disease is > 1 cm. Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed. This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a randomized trial of intense versus standard chemotherapy. STUDY DESIGN: Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses, respectively. There was no difference in progression-free interval or survival between the two arms. Of the 458 stage III (with residual disease > 1 cm) and stage IV patients entered in this study, 294 stage III patients comprise the current analysis. Surgical reporting forms, operation reports, and pathology reports were reviewed to determine initial greatest tumor diameter and residual tumor diameter. Patients were grouped by residual diameter. Multivariate analysis considered residual diameter of disease, age, histologic characteristics, performance status, and ascites. An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group. RESULTS: Patients ranged in age from 20 to 80 years, with a median of 60 years. All patients were Gynecologic Oncology Group performance status 0 to 2. Fifty-two percent had grade 3 tumors, and 39% and 9%, respectively, had grade 2 or 1 tumors. All patients had stage III disease. Ninety percent had serous, endometrioid, or mixed epithelial cell type tumors. Multivariate analysis revealed a relative risk of dying as follows: residual disease < 2 cm, relative risk 1.00; 2 to 2.9 cm, relative risk 1.90; 3 to 3.9 cm, relative risk 1.91; 4 to 5.9 cm, relative risk 1.74; 6 to 7.9 cm, relative risk 1.85; 8 to 9.9 cm, relative risk 2.16; > or = 10 cm, relative risk 1.82. The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant (p < 0.01). There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm. CONCLUSIONS: Among patients with suboptimal (> 1 cm residual disease) epithelial ovarian cancer, those who have small diameter residual disease (< 2 cm) tend to survive longer than those who have larger residual disease. Among those with larger residual disease, size does not affect prognosis appreciably.

Adult↗
PubMed1994

Development of single-agent chemotherapy regimens for gestational trophoblastic disease.

Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is most successful for patients who have had an antecedent molar pregnancy with a plateau or persistent beta-human chorionic gonadotropin elevation after molar evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has been associated with high cure rates, as has methotrexate with citrovorum factor rescue, which reduces toxicity. Standard definitions of low-risk gestational trophoblastic disease and response assessment are critical to a comparison of prognostic features related to single-agent therapy success. Methotrexate with folinic acid rescue administered as primary therapy does achieve an excellent therapeutic outcome with limited chemotherapy exposure but at increased cost. The weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is inexpensive and allows close monitoring of disease status. Single-dose or pulsed actinomycin-D provides a high level of complete response, although gastrointestinal toxicity, mainly nausea and vomiting, is quite common. Management of first-line chemotherapy failures is unclear, although in the GOG methotrexate trial it was evident that another agent, such as actinomycin-D, should be used to provide the highest success rate. The use of a single agent in low-risk metastatic trophoblastic disease (lung and/or vaginal metastases) depends upon restricting it to patients who have not failed prior chemotherapy, have a low World Health Organization score and have no evidence of the presence of choriocarcinoma, but a much higher first-line failure rate should be anticipated than in nonmetastatic disease. Other single-agent regimens have been proposed that are worthy of investigation to create a safer, more efficacious and more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1994

Prognostic factors in surgical stage III and IV carcinoma of the endometrium.

OBJECTIVE: To identify prognostic factors in surgical stage III and IV endometrial carcinoma. METHODS: We performed a retrospective analysis of 58 cases of stage III and IV endometrial cancer using the Cox proportional hazards model. RESULTS: Extrapelvic peritoneal metastases and positive peritoneal cytology greatly affected survival. If either of these factors was present, the 2-year survival rate was only 25%, whereas if they were absent, it was 82%. All patients with extrapelvic metastases died of their disease despite systemic therapy, as did ten of 13 patients with positive peritoneal cytology. Although postoperative therapy in these patients varied, it had no obvious effect on survival or on the site of recurrence. In the absence of abdominal disease or positive peritoneal cytology, survival was not influenced significantly by the presence or absence of lymph node metastases. The difference in survival between women with aortic and pelvic lymph node metastases (24% at 5 years) was not significant, but the power to detect this difference was low (35%). Stage affected survival significantly (P < .05), but a two-category variable, indexing patients as having either positive peritoneal cytology or abdominal disease, provided a much better fit and a more parsimonious model for the data. CONCLUSION: Five-year survival rates exceeding 70% can be achieved in endometrial carcinoma even if extrauterine disease is present, provided that peritoneal cytology is negative and abdominal metastases are absent.

Aged↗
PubMed1993

Localized ovarian cancer in the elderly. The Gynecologic Oncology Group experience.

BACKGROUND: The appropriate therapy for patients with localized (FIGO Stage I and II) ovarian cancer has been poorly defined for all age groups and particularly for the elderly. Few prospective randomized comparisons of adjuvant therapy after careful surgical staging have been performed. The Gynecologic Oncology Group (GOG) has performed a series of trials testing adjuvant treatment in carefully staged patients with early-stage ovarian cancer. Early trials included few elderly patients but the most recent trial (GOG 95) included 18% over the age of 65 years. METHODS: Comprehensive surgical staging defined by protocol is performed before randomization. Patients with predefined stages and histologies are included and the patients are randomized prospectively to receive either intraperitoneal phosphorus-32 or three monthly cycles of cyclophosphamide and cisplatin. Assessment of the value of this adjuvant therapy will depend on survival, disease-free survival, and relapse pattern differences between the two adjuvant therapies. RESULTS: This is an ongoing clinical trial and insufficient numbers of patients have been randomized for definitive conclusions. There have been seven recurrences on both arms of the trial with a median time to recurrence of 14 months. There currently are no significant age differences between relapsed patients and disease-free patients. At this point, 12 elderly patients have been randomized to each of the arms of therapy. CONCLUSIONS: Although no apparent survival differences exist for elderly patients in the most recent adjuvant chemotherapy trial of early ovarian cancer, the number of patients with cancer randomized and follow-up are insufficient to establish such a difference. Currently there is no evidence that elderly patients display a significant difference in relapse frequency or pattern.

Adult↗
PubMed1993

Combined antiproliferative activity of 5-fluorouracil and mitomycin-C against primary human ovarian tumors and cell lines in a clonogenic assay.

Ovarian tumors from 389 patients were successfully grown in a human tumor clonogenic assay (HTCA). Specimens from patients with or without prior chemotherapy showed similar chemosensitivity patterns. Excluding drugs commonly used for first-line chemotherapy, 5-fluorouracil (5-FU) and mitomycin-C (MMC) are among the active second-line agents, based upon HCTA data. Using this in vitro information from primary tumor specimens, two human ovarian cancer cell lines were used to study in detail the interactions of combined 5-FU and MMC. Drug scheduling which maximized combined antitumor activity was studied. Combined 5-FU and MMC revealed positive drug interactions most consistently when both drugs were used simultaneously with long-term exposure. Pulse treatment with MMC (1 hr) followed by continuous 5-FU exposure resulted in slightly less additive interaction than simultaneous long-term exposure. Pretreatment with 5-FU followed by a continuous exposure to MMC was as effective as the simultaneous method, as long as MMC was added within an 8-hr interval. Drug schedule dependency was examined, revealing that MMC, as a single agent, is both dose and schedule dependent. The results of these in vitro studies suggest that: (1) exposure to prior chemotherapy does not induce demonstrable pleiotropic drug resistance in these ovarian cancers tested; and (2) combined 5-FU and MMC show positive interactions against ovarian cancer cell lines, with optimal scheduling seeming to be long-term simultaneous exposure to both MMC and 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva (a Gynecologic Oncology Group study)

From 1977 to 1984 the Gynecologic Oncology Group (GOG) conducted a prospective clinical and surgical staging protocol of squamous cell carcinoma of the vulva (n = 637). The patients with superficial (5 mm or less invasion) lesions were the subject of a previous report (n = 272). The subject of this report is on factors that predict groin node metastasis based on all 588 evaluable patients. Comparisons between the two reports are made. Almost half of this group (49.3%) had minimal tumor thickness (< or = mm). Almost one-third of patients had small vulvar lesions (< or = cm). Groin node metastasis was 18.9% for the < or = 2-cm diameter tumors and 41.6% for the > 2-cm diameter lesions. The inaccuracy of clinical palpation of the groin nodes (23.9% false negative) largely accounts for underestimation of extent of disease. Body weight was not related to the sensitivity of detecting positive groin nodes (P = 0.26). Using the logistic model, independent predictors of positive groin nodes were identified (in order of importance): less tumor differentiation by GOG criteria (P < 0.0001), suspicious or fixed/-ulcerated nodes (P < 0.0001), presence of capillary-lymphatic involvement (P < 0.0001), older age (P = 0.0002), and greater tumor thickness (invasion) (P = 0.03). Lesion size and location were not independent predictors of positive groin nodes.

Aged↗
PubMed1993

Steroid receptor concentrations in endometrial carcinoma: effect on survival in surgically staged patients.

Estrogen and progesterone receptor concentrations were measured in the primary tumors of 137 surgically staged women with clinical stages I and II endometrial carcinoma. For each steroid, increasing receptor concentrations were associated with a decrease in hazard (increase in survival) and the effect was linear for each receptor. When expressed dichotomously, steroid receptor status was also significantly associated with a number of known risk factors, and the significance of the association was influenced by the receptor concentration used as the criterion for receptor positivity. In a multivariate analysis, only progesterone receptor concentration affected survival independently, but the effect disappeared when the analysis was restricted to women with disease confined to the uterus. We conclude that the estrogen and progesterone receptor status of the primary tumor is of limited prognostic significance in endometrial carcinoma unless extrauterine disease is present.

Adenocarcinoma↗
PubMed1993

Antiestrogenic potency of toremifene and tamoxifen in postmenopausal women.

In this nonblinded, controlled multicenter trial, postmenopausal women were randomly assigned to receive graded doses of toremifene and tamoxifen or no antiestrogen to assess dose-response levels and evaluation methodology. For standardization, transdermal estradiol (Estraderm-Ciba Geigy) was applied to all women for 38 days. The antiestrogens were added on days 29-38. For control and all treatment groups, there were no significant changes in serum chemistries or serum hormone levels, nor were there differences in adverse effects. The use of continuous estradiol precluded any meaningful assessment of the estrogenicity of tamoxifen or toremifene. As measured by vaginal superficial cytologic cell count changes, the antiestrogenic activity of toremifene doses ranging from 20 to 200 mg/day could not be distinguished from that of 20 mg/day of tamoxifen, the clinically recommended dose in North America.

Adult↗
PubMed1993

Randomized comparison of the antiemetic efficacy of a serotonin type 3 receptor antagonist (MDL 72,222) with a high-dose metoclopramide regimen.

This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted.

Adult↗
PubMed1993

Circadian-timed combination doxorubicin-cisplatin chemotherapy for advanced endometrial carcinoma. A phase II study of the Gynecologic Oncology Group.

Patients with advanced or recurrent endometrial cancer of any cell type having measurable disease have been entered into this study to determine the effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy. This Phase II study involved no randomization with treatment initiated with doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2 over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients without progression. Thereafter, responders continued on cisplatin alone. A review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%) partial responses, and 7 (23%) with stable disease. The number of treatment courses ranged from 2 to 14 with a median of 6.5. the median white blood cell nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300-3,600/mm3) For the 16 patients experiencing thrombocytopenia the median nadir was 48,500/mm3 (range: 8,000-138,000/mm3). There were no treatment-related deaths. Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably well tolerated and demonstrated notable response rates in patients with advanced or recurrent endometrial carcinoma.

Adult↗