Biomedical subjects

B N Bundy

Publications and source records attributed to B N Bundy.

At least 19 recordsLinked to original sources

PubMed2001

Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.

PURPOSE: To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin. PATIENTS AND METHODS: Patients were randomized to receive either IV paclitaxel 135 mg/m(2) over 24 hours followed by IV cisplatin 75 mg/m(2) every 3 weeks for six courses or IV carboplatin (area under curve 9) every 28 days for two courses, then IV paclitaxel 135 mg/m(2) over 24 hours followed by intraperitoneal (IP) cisplatin 100 mg/m(2) every 3 weeks for six courses. RESULTS: Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received < or = two courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 v 22 months; relative risk, 0.78; log-rank P =.01, one-tail). There was a borderline improvement in overall survival associated with this regimen (median, 63 v 52 months; relative risk, 0.81; P =.05, one-tail). CONCLUSION: An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, the experimental arm is not recommended for routine use. However, the results provide direction for further clinical investigation in small-volume ovarian cancer.

Aged↗

PubMed1999

Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.

BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3). RESULTS: The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively. CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.

Adult↗

PubMed1999

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Adult↗

PubMed1999

Bleomycin, etoposide, and cisplatin combination therapy of ovarian granulosa cell tumors and other stromal malignancies: A Gynecologic Oncology Group study.

OBJECTIVES: The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies. METHODS: Patients with incompletely resected Stages II-IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2 x 9 weeks for a maximum dose of </=30 units x 9) was changed, without subsequent mortality. The final dose schedule was 20 units/m2 bleomycin iv push day 1 every 3 weeks x 4, 75 mg/m2 etoposide days 1-5 every 3 weeks x 4 and 20 mg/m2 cisplatin days 1-5 every 3 weeks x 4. The frequency of negative second-look surgery was the primary outcome measure. RESULTS: Seventy-five women were entered; 18 were excluded. Grade 4 myelotoxicity occurred in 61% of the patients. The end point used for response was negative second-look laparotomy. Thirty-seven percent (14/38) of the patients undergoing second-look laparotomy had negative findings. The six complete responders were of long median duration (24.4 months). Patients with measurable disease were at the highest risk of progression and death. CONCLUSIONS: BEP appears to be an active combination regimen for first-line chemotherapy of malignant tumors of the ovarian stroma. Myelotoxicity was tolerable.

Adult↗

PubMed1999

A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study.

OBJECTIVE: The objective of this study was to evaluate the benefits and risk of adjuvant pelvic radiotherapy aimed at reducing recurrence in women with Stage IB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: Two hundred seventy-seven eligible patients were entered with at least two of the following risk factors: >1/3 stromal invasion, capillary lymphatic space involvement, and large clinical tumor diameter. Of 277 patients, 137 were randomized to pelvic radiotherapy (RT) and 140 to no further treatment (NFT). RESULTS: Twenty-one (15%) in the RT group and 39 (28%) in the NFT group had a cancer recurrence, 18 of whom were vaginal/pelvic in the RT and 27 in the NFT group. In the RT group, of 18 (13%) who died, 15 died of cancer. In the NFT group, of the 30 (21%) who died, 25 died from cancer. Life table analysis indicated a statistically significant (47%) reduction in risk of recurrence (relative risk = 0.53, P = 0.008, one-tail) among the RT group, with recurrence-free rates at 2 years of 88% versus 79% for the RT and NFT groups, respectively. Severe or life-threatening (Gynecologic Oncology Group grade 3 or 4) urologic adverse effects occurred in 4 (3.1%) in the RT group and 2 (1.4%) in the NFT group; 3 (2.3%) and 1 (0.7%) hematologic; 4 (3.1%) and 0 gastrointestinal (GI); and 1 (0.8%) and 0 neurologic, respectively. One patient's death was attributable to grade 4 GI adverse effects. CONCLUSIONS: Adjuvant pelvic radiotherapy following radical surgery reduces the number of recurrences in women with Stage IB cervical cancer at the cost of 6% grade 3/4 adverse events versus 2.1% in the NFT group.

Adult↗

PubMed1999

Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.

PURPOSE: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities. METHODS: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU. RESULTS: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018). CONCLUSION: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.

Adenocarcinoma↗

PubMed1998

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study.

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Hydroxyurea, 5-fluorouracil infusion, and cisplatin adjunct to radiation therapy in cervical carcinoma: a phase I-II trial of the Gynecologic Oncology Group.

BACKGROUND: In a previous study, the Gynecologic Oncology Group (GOG) compared hydroxyurea (HDXR) and the combination of cisplatin (C) and 5-fluorouracil (5-FU) infusion as potentiators of radiation therapy. This study was undertaken to determine whether these two regimens could be combined, concurrent with pelvic radiation therapy in patients with locally advanced cervical cancer. METHODS: The GOG entered 75 eligible and evaluable patients on a Phase I-II evaluation of HDXR, C, and 5-FU as adjuncts to radiation therapy for locally advanced carcinoma of the cervix. All patients had histologically verified primary disease and confirmed negative para-aortic lymph nodes. Eligibility was limited to clinical stage IIB through IVA. HDXR was given orally, twice weekly at a dose of 2.5 g/m2; C on Days 1 and 29 at 50 mg/m2; and 5-FU by 96-hr infusion on Days 2-5 and 30-33 at a starting dose of 800 mg/m2. RESULTS: Forty-eight (64%) patients had stage IIB disease, 25 (33%) had stage IIIB, and 2 had stage IVA tumors. Primary tumors 4 cm or less in size were present in 15 patients, between 4 and 6 cm were in 27 patients, and larger than 6-cm were observed in 33 patients. Grade 3/4 acute toxicity was experienced by 41 (54.7%) patients. These acute toxicities caused delays in prescribed radiation therapy of more than 1 week in 14 (18.9%) and low doses of drug in 16 (21.3%), and only 26 (34.7%) patients had the scheduled dose escalation of 5-FU on their second course. Clinical response was excellent with complete and partial response rate of 93.3%. Median time to progression has not been reached. CONCLUSION: Although this dose and schedule could be successfully administered, the delays in therapy should be avoided by a lower starting dose of hydroxyurea. Stomatitis was not a dose-limiting toxicity. These results have formed the basis of a phase III trial comparing this regimen to two other chemoradiation regimens.

Adult↗

PubMed1996

Sites of failure and times to failure in carcinoma of the vulva treated conservatively: a Gynecologic Oncology Group study.

OBJECTIVE: The objective of this review was to examine the patterns of failure after conservative therapy for vulvar carcinoma to establish a basis for the design of prospective cooperative trials in this disease. STUDY DESIGN: The records and characteristics of all patients in whom cancer recurred after conservative therapy in two prospective clinical trials were analyzed. RESULTS: Of 143 patients who received one or more modifications of therapy, 37 patients had recurrence of cancer and 20 died of the disease. The median intervals to recurrence were 35.9 months for vulvar cancer and 7.0 months for groin cancer (p = 0.0002). There were 12 groin recurrences; 11 (91.7%) of these patients have died of the disease. The median survival time after recurrence was 52.4 months for patients with vulvar cancer and 9.4 months for those with groin cancer (p = 0.0025). CONCLUSIONS: Groin cancer recurs earlier than vulvar cancer among patients treated conservatively. Future trials that evaluate modified therapy to the groin need to include early interim analyses. Follow-up for > 36 months after study entry may not be necessary to evaluate the impact of new treatments.

Adult↗

PubMed1994

Malignant melanoma of the vulva treated by radical hemivulvectomy. A prospective study of the Gynecologic Oncology Group.

BACKGROUND: Beginning in 1983, the Gynecologic Oncology Group (GOG) conducted a prospective clinicopathologic study of primary malignant melanoma of the vulva. The objectives of this study were to determine the relationship of histopathologic parameters and microstaging to the International Federation of Gynaecology and Obstetrics (FIGO) staging and prognosis. METHODS: All patients with primary untreated malignant melanoma of the vulva and no history of previous or subsequent other primary invasive malignancy were eligible for study entry. All patients were required to have modified radical hemivulvectomy as minimal therapy. Groin dissection was optional. Histopathologic specimens were reviewed for capillary space involvement, Clark's level, Breslow's depth of invasion, cell type, and melanin distribution. Patient characteristics were analyzed in their relationship to groin node status and recurrence-free interval. RESULTS: Between 1983 and 1990, 81 patients were entered in the study. Of these, 71 were evaluable. Thirty-four patients underwent radical hemivulvectomy, and 37 patients underwent radical vulvectomy. In addition, 56 patients underwent groin node dissection. The factors that were independently correlated with groin node status were: capillary lymphatic space involvement (p = 0.0001) and central primary tumor location (i.e., bilateral/clitoral/T3) (P = 0.003). The other factors that were significant--clinical tumor size, vulvar staging (FIGO), GOG performance status, and Breslow's depth of invasion--were not independent predictors of positive nodes. The factor with the highest significant correlation with recurrence-free interval was the 1992 staging system of the American Joint Committee on Cancer (AJCC) for malignant melanoma of the skin. Using multiple regression, AJCC stage was the only independent prognostic factor. In the absence of AJCC stage, Breslow's depth of invasion was the most prognostic. CONCLUSION: The biologic behavior of vulvar melanoma is similar to other nongenital cutaneous malignant melanoma.

Adult↗

PubMed1994

The prognostic value of nuclear versus architectural grading in endometrial adenocarcinoma: a Gynecologic Oncology Group study.

The pathologic grade of endometrial adenocarcinoma is widely recognized as an important prognostic and therapeutic indicator. However, disagreement persists about the optimal method of determining grade. The pathology committee of the Gynecologic Oncology Group employs a system based on the proportion of tumor in glandular array; this system is both reproducible and predictive of outcome. Others have suggested that grading based on nuclear pleomorphism and the size of nucleoli provides better prognostication. We compared the three-level architectural grading system (AG) with a two-level nuclear grading system (NG) to determine reproducibility and prognostic value in 88 cases of stage 1 endometrial adenocarcinoma. Three pathologists made independent assessments of grade by each method. The division of tumors by architectural arrangement was superior for predicting survival (83%, 73%, and 44%, AG, p = 0.005; vs. 79% and 61%, NG, p = 0.14) and equivalent to nuclear grading for prediction of recurrence. Both systems were moderately reproducible (k = 0.49, AG; k = 0.57, NG). Assessment of NG was more tedious than that of AG. Subdivision of architectural grade based on high nuclear atypia, as recommended in current, International Federation of Gynecology and Obstetrics guidelines, did not improve prognostication. Because grading based on nuclear pleomorphism does not provide prognostic information superior to that resulting from architectural grading, we do not advocate its use in routine surgical pathology practice.

Adenocarcinoma↗

PubMed1994

Evaluation and comparison of histopathologic grading systems of epithelial carcinoma of the uterine cervix: Gynecologic Oncology Group studies.

The subjects of this study are 445 patients with advanced cervical cancer treated by standardized radiation therapy. Upon entry into one of two Gynecologic Oncology Group (GOG) protocols, original pathologic diagnoses and histologic tumor descriptions for each patient were compared with separate evaluations made by a consensus opinion of two GOG pathologists. A review diagnosis using grade, cell type, and the Stendahl scoring system was then made by the first author (R.J.S.) without knowledge of the prior diagnoses. Of the original pathologists' diagnoses, 21% did not include grade or cell type. There was little agreement among the different pathologists as to the use of either specific grade or cell type. Histologic grade, irrespective of the pathologists making the diagnosis, had no correlation to prognosis. The Reagan and Wentz large-cell keratinizing (LCK) cell type, when applied by the author to tumors with any form of squamous keratinization present, identified a group of patients with a poorer prognosis, although not independently of other prognostic factors. The Stendahl scoring system identified a number of patients with both a poorer and better prognosis. This was statistically significant and independent of other risk factors. A major limitation, however, was the number of patients evaluable because of inadequate biopsy material in 23.6% of the study group.

Adult↗

PubMed1993

Carcinoma of the cervix treated with chemotherapy and radiation therapy. Cooperative studies in the Gynecologic Oncology Group.

Since its inception in 1970, the Gynecologic Oncology Group (GOG) has pursued a series of Phase II and III cooperative clinical investigations of the combination of cytotoxic chemotherapy and radiation therapy for patients with locally advanced carcinoma of the cervix. After an initial randomized trial indicated that hydroxyurea was superior to placebo, subsequent studies have evaluated whether the hypoxic sensitizer, misonidazole, or the combination of cisplatin with infusional 5-fluorouracil were superior to hydroxyurea. Other studies have evaluated concurrent chemotherapy with extended field radiation for patients with metastatic disease in their paraaortic nodes. The GOG will continue to attempt to identify and develop superior adjuncts to radiation therapy for this patient population.

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

A phase II trial of medroxyprogesterone acetate in epithelial ovarian cancers. A Gynecologic Oncology Group study.

Twenty-four evaluable patients with advanced or recurrent epithelial ovarian carcinoma who progressed on platinum-containing combination chemotherapy were treated with medroxyprogesterone acetate (C.T. Provera) 50 mg orally three times a day until progression of disease. One patient had a partial response (4.2%), 9 patients had stable disease (37.5%), and 14 (58.3%) had increasing disease. The 95% upper confidence limit for response is less than or equal to 18.3%. There was no toxicity associated with its use. C.T. Provera has limited activity in patients with epithelial ovarian cancer who have failed combination chemotherapy.

Adult↗

PubMed1993

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

PURPOSE: Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS: Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS: There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION: In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

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

The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study.

Gynecologic Oncology Group Protocol 52, a randomized trial of cisplatin and cyclophosphamide with or without doxorubicin in "optimal" Stage III epithelial ovarian cancer, failed to demonstrate a significant difference in the outcome in 349 evaluable patients. Additional review of the records was carried out to determine the influence of cytoreductive surgery on survival. Since eligibility for the study was the presence of residual cancer of 1 cm or less, the influence of cytoreductive surgery could be evaluated by comparing outcome in patients presenting with large-volume extrapelvic disease, but who were cytoreduced to small-volume disease. Factors evaluated were age, cell type, grade, size, and location of disease at exploration, size, and location of residual disease after cytoreduction, number of residual nodules, ascites, type of surgery, blood loss, and hospital days. Univariate analysis revealed that age, size of residual disease, mucinous or clear cell histologic type, histologic grade, and number of residual lesions were significant prognostic factors. By univariate analysis patients found to have extrapelvic disease of 1 cm or less had a better recurrence-free interval and survival than those patients with large-volume disease who were cytoreduced to disease of 1 cm or less. Multivariate analysis revealed that older age, histologic grades 2 and 3, and 20 or more residual lesions were unfavorable. The volume of initial extrapelvic disease remained significant when gross disease was present in the omentum and in other extrapelvic sites. This study failed to prove the hypothesis that initial cytoreductive surgery would allow a patient presenting with large-volume ovarian cancer to have the same chance for survival as a patient found to have small-volume disease. Factors other than cytoreductive surgery are important in predicting survival.

Adult↗