Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity.

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

Treatment of metastatic stromal tumors of the ovary with cisplatin, doxorubicin, and cyclophosphamide.

From September 1981 until June 1986, eight patients with metastatic ovarian stromal tumors were entered into a prospective phase II study to determine the efficacy of a chemotherapy regimen combining cisplatin, doxorubicin, and cyclophosphamide. Patients received cisplatin 40-50 mg/m2 intravenously (IV), doxorubicin 40-50 mg/m2 IV, and cyclophosphamide 400-500 mg/m2 IV, all on day 1 every 28 days. The median age was 43 years (range 24-65 years). Two patients had stage II disease, one had stage III, and five had recurrent disease (original stage: four stage I and one stage III). The median number of chemotherapy cycles was six (range four to 14). Three patients (38%) had a complete response to therapy (two confirmed by second-look laparotomy), and two patients (25%) achieved a partial response (one verified by second-look laparotomy). The overall response rate was 63%. Toxicity was minimal. Four patients are disease-free at 13+ to 48+ months, one patient is alive with disease at six+ months, and three patients are dead of tumor at four, 17, and 36 months from the start of chemotherapy. These results indicate that the combination of cisplatin, doxorubicin, and cyclophosphamide has modest activity in the treatment of metastatic ovarian stromal tumor.

Cervical adenocarcinoma: tumor implantation in the episiotomy sites of two patients.

The spread of cervical carcinoma associated with parturition through a tumorous cervix is rarely demonstrated. This report details two patients with adenocarcinoma of the cervix who delivered term fetuses vaginally and subsequently presented with tumor nodules in the episiotomy scars. Although both patients appear to have had their recurrences treated successfully, follow-up on one patient has been only 10 months since the completion of therapy. Tumor implantation of the episiotomy wound is a potential risk associated with vaginal delivery in a pregnant patient with cervical carcinoma. However, this iatrogenic mechanism of tumor spread may permit an opportunity for successful treatment of the local recurrence.

Preoperative radiotherapy for early endometrial carcinoma.

A retrospective study was undertaken to compare the use of one versus two preoperative radium systems for early endometrial carcinoma. The charts of 73 patients treated between 1977 and 1980 were reviewed. No difference was noted between the two groups when compared for stage, grade, depth of myometrial invasion, and histologic type of tumor. One of thirty-eight (2.6%) patients in the one-radium group developed an isolated central recurrence; there were no central recurrences in the two-radium group. Total duration of therapy and total hospitalization for the one-radium versus the two-radium group were 17.6 and 15.3 days versus 77.0 and 17.3 days, respectively. Follow-up ranged from 48 to 84 months. Corrected survival figures are comparable to 94.6% for the one-radium group versus 100% for the two-radium group. These data suggest comparable effectiveness and morbidity between the two treatment regimens, with the single-radium application more efficient and cost effective.

A trial of continuous-infusion vinblastine in refractory endometrial adenocarcinoma.

Fourteen patients with refractory or metastatic adenocarcinoma of the endometrium were treated with continuous infusion vinblastine. No patient had a response. One patient had stable disease. Although well tolerated, vinblastine sulfate given by this method has no activity in this malignancy.

Cisplatin, vinblastine, and bleomycin combination therapy in resistant gestational trophoblastic disease.

Eleven patients were treated with cisplatin, vinblastine, and bleomycin (PVB) combination chemotherapy after failure of conventional triple-agent therapy with methotrexate, dactinomycin, and cyclophosphamide for gestational trophoblastic disease. Of ten evaluable patients, five (50%) achieved negative titers. Sustained remission was achieved in only two patients (20%). Major hematologic toxicities and two deaths due to sepsis occurred in this group of patients. Although this combination does exhibit activity, its clinical use in the treatment of refractory trophoblastic disease is limited.

Palliation of small bowel obstruction by percutaneous gastrostomy in patients with progressive ovarian carcinoma.

Percutaneous gastrostomy is a useful palliative technique for treatment of patients with bowel obstructions in advanced ovarian carcinoma. A description of the technique is presented along with a review of ten cases in which the procedure was used at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. In all patients, the procedure was well tolerated and associated with little morbidity. In applicable cases, percutaneous gastrostomy appears to be superior to both nasogastric suction and operative gastrostomy for palliation of small bowel obstruction in terminal ovarian cancer.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin.

Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo-oophorectomy in ten patients, and bilateral salpingo-oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second-line treatment; three patients had a complete response to therapy and are surviving disease-free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide-containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short-term combination regimen that has promising activity against malignant germ cell tumors of the ovary.

Urinary conduits in gynecologic oncology.

Over an 11-year period (1971 to 1981), 212 urinary conduit surgeries were performed by the Department of Gynecology at the University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston. The urinary diversions were performed as part of the pelvic exenteration operation in 154 patients, for radiation injury in 48 patients, and for palliation of disease recurrence in ten patients. Ninety-three percent had prior pelvic radiotherapy. Various segments of the gastrointestinal tract were used, including the ileum (102), sigmoid colon (99), transverse colon (four), jejunum (four), and others (three). Fifty percent of abnormal preoperative intravenous pyelograms reverted to normal after urinary diversion. Revision of the stoma was required in 6%. Other complications included infection (18%), renal loss (17%), and urinary leaks and fistulae (3%). The overall perioperative mortality was 7%, decreasing from 11% in the first five years to 3% during the last six years. Ureteral stents were routinely used. When selecting a segment of bowel for a urinary conduit, both tissue quality and mobility are important. Mortality and morbidity of urinary conduit surgery continues to decrease with experience.

A phase II trial of 4-demethoxydaunorubicin in refractory epithelial ovarian cancer.

Sixteen evaluable patients with refractory epithelial ovarian cancer were treated with oral 4-demethoxydaunorubicin. The drug was given in divided doses over 5 days and dosage was repeated every 3 weeks. There were no objective remissions. Three patients had stabilized disease of 5 to 7 months duration. Although well tolerated, this anthracycline has modest effectiveness against previously treated ovarian cancer.

Ethinyl estradiol and medroxyprogesterone acetate in patients with epithelial ovarian carcinoma: a phase II study.

Patients with ovarian carcinoma refractory to chemotherapy received a sequential combination of ethinyl estradiol and medroxyprogesterone acetate in two dose regimens. There was no difference in therapeutic activity of the two dose regimens. Of 65 patients, nine (14%) responded to treatment and 13 (20%) had stable disease. Vascular complications occurred in three patients; hemiplegia developed in one of those. Nine patients had significant nausea and vomiting, and one experienced severe depression that required treatment withdrawal. The sequential and combined use of ethinyl estradiol and medroxyprogesterone acetate may provide an alternative treatment for certain patients with ovarian carcinoma that does not respond to optimum chemotherapy. Additional studies are required to determine if synergism exists between this treatment and other modalities of therapy. Further investigation is required into the vascular disorders that complicate therapy to determine whether appropriate preventive measures are possible.

Adenoid cystic carcinoma of Bartholin gland.

Five cases of adenoid cystic carcinoma of the Bartholin gland, a rare vulvar tumor, are reviewed with respect to clinical and pathological characteristics. Histologic transition from normal Bartholin gland to adenoid cystic carcinoma was evident in two cases. Two patients developed the tumor in association with pregnancy. Local recurrences are common and may precede distant metastases, pulmonary being the most common. Patients with repetitive local recurrence or pulmonary metastases may have slowly progressive disease and survive for many years. This is reflected in the disparity between the progression-free interval and survival curves. The recommended primary treatment is wide local excision, obtaining clear margins, and an ipsilateral inguinal lymphadenectomy.

A phase II trial of bisantrene (CL216,942) in refractory epithelial ovarian cancer.

Twenty-three evaluable patients with refractory epithelial ovarian cancer were treated with bisantrene (CL216,942). The drug was given as a single-dose injection every 3 weeks. One patient (4%) showed a partial response. The compound thus has limited activity against this malignancy.

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vincristine, dactinomycin, and cyclophosphamide.

Eighty patients with malignant nondysgerminomatous germ cell tumors of the ovary were treated with the combination of vincristine, dactinomycin, and cyclophosphamide (VAC) at The University of Texas M.D. Anderson Hospital and Tumor Institute. All patients underwent initial surgery: biopsy alone in 3 patients, unilateral salpingo-oophorectomy in 48 patients, and bilateral salpingo-oophorectomy with or without hysterectomy in 29 patients. Sixty-six patients received VAC as primary postoperative therapy; 46 patients (70%) achieved a sustained remission. VAC produced sustained remission in 86% of patients with Stage I, 57% of patients with Stage II, 50% of patients with Stage III, and no patients with Stage IV disease. For patients with Stage I disease, survival rates did not differ among histologic groups, but in advanced disease, patients with immature teratoma did significantly better than the others. Four of the 20 patients who failed primary VAC therapy were salvaged with other therapies, and 8 of 14 treated with VAC after relapse or failure of other treatments were salvaged. Although VAC produces excellent results with very acceptable toxicity in patients with Stage I disease and advanced immature teratoma, survival of patients with other advanced histologic types has been disappointing. The authors are therefore treating this latter group with alternative therapy such as vinblastine, bleomycin, and cisplatin with the goal of achieving improved efficacy.

Sarcoma botryoides of the female genital tract.

Results of treating 14 patients with sarcoma botryoides of the female genital tract are reviewed. Nine patients were younger than four years old and five were older than 14. Primary tumors were in the vagina (eight), cervix (three), vulva (one), and cervicovaginal region (two). All but one patient underwent surgery, including wide local excision (one), vaginectomy (one), hysterectomy (one), hysterectomy and vaginectomy (two), anterior exenteration (two), and total pelvic exenteration (six). A combination of vincristine, actinomycin-D, and cyclophosphamide was the chemotherapy regimen most frequently administered. Only one of the nine patients receiving chemotherapy died from recurrence. One patient with disease too extensive for surgery received intraarterial vincristine and radiation therapy; 16 years later she developed an adenosquamous carcinoma of the uterus. Sarcoma recurred in three patients. This review of patients treated between 1956 and 1983 reflects the evolution of therapy over 30 years. Conservative surgery alone was inadequate; therefore, radical (exenterative) surgery was adopted; recently less extensive surgery has been combined with chemotherapy, producing satisfactory results.

Alveolar rhabdomyosarcoma of the female genitalia.

Eight cases of alveolar rhabdomyosarcoma of the female genitalia were diagnosed from 1963 to 1983 at The University of Texas M. D. Anderson Hospital. The primary sites were vulva in two, perineum in five, and broad ligament in one patient. When possible, therapy was initiated with local tumor excision (five patients). Surgery was followed by local or regional radiation (six patients) and chemotherapy (seven patients). Of the eight patients, five died within 9 months, one died 27 months after diagnosis, and only two are 5-year survivors. The aggressive behavior of this tumor is evidenced by autopsy findings of widespread metastases. Metastatic disease to the bone was present in four patients and to the breast in three patients. Local disease was controlled in two patients who died of distant metastases. Current therapy recommendations include excisional surgery, local radiation, and combination chemotherapy. A need for more effective chemotherapeutic programs is evident.

Endodermal sinus tumor of the vagina and cervix.

This report describes six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls younger than age 3 years simulates the presentation of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin-D, and cyclophosphamide (VAC) for 11 months. This is the first report of such a response. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This is the first report of apparently successful therapy that allowed retention of childbearing potential. Four of the six patients have been disease-free from 2 to 23 years. After examining the world literature, it is concluded that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects.

Continuous-infusion vinblastine in refractory carcinoma of the cervix: a phase II trial.

Twenty patients with recurrent or metastatic squamous cell carcinoma of the cervix were treated with continuous-infusion vinblastine sulfate. Two patients (10%) had partial responses of 4 and 7 months' duration. Neutropenia was dose limiting. Vinblastine sulfate given by continuous infusion has limited activity in this malignancy.