Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study.

Ninety-six assessable patients with advanced or recurrent uterine sarcomas, who were no longer controllable with surgery and radiotherapy, and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Of 63 cases with mixed mesodermal tumors, five complete responses (CRs; 8%) and seven partial responses (PRs; 11%) were observed (95% confidence interval [CI], 10.3% to 30.9%). Of 33 patients with leiomyosarcoma, one PR (3%) was observed (95% CI, .1% to 15.8%). Adverse effects included leukopenia (23%), nausea and vomiting (73%), and mild azotemia (42%). No patients experienced life-threatening toxicity. Cisplatin has definite activity when given at the dose and schedule that we tested for patients with mixed mesodermal sarcomas who have not received prior chemotherapy, but has little activity in patients with leiomyosarcoma.

A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.

PURPOSE: From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS: Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS: Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION: The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.

Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.

Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study.

PURPOSE: From December 1983 through February 1992, a prospective study designed to determine the clinical course of patients with ovarian tumors of low malignant potential (LMP) was conducted by the Gynecologic Oncology Group (GOG). MATERIALS AND METHODS: This protocol was developed to evaluate the following (1) the biologic behavior of ovarian LMP tumors, (2) the effectiveness of melphalan chemotherapy in patients with clinically detectable residual disease after surgical staging and in patients whose tumors progress or recur after surgical therapy, and (3) the response rate to cisplatin in those who failed to respond to melphalan therapy. The study group consisted of 146 assessable patients with stage I serous LMP tumors. All of these women had the affected ovary (or ovaries) removed, and a complete staging operation was performed in each case. While 123 patients had a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), 21 retained the uterus and one normal-appearing ovary and fallopian tube. No adjuvant chemotherapy or radiation therapy was administered to any patients in the stage I study group. RESULTS: The median follow-up time was 42.4 months (range, 1.6 to 108). Thus far, no patient with a stage I ovarian serous LMP tumor has developed recurrent disease. CONCLUSION: Stage I ovarian serous LMP tumors rarely, if ever, recur. Limited resection, after meticulous surgical exploration, is adequate therapy for women of reproductive age.

Salvage whole abdomen radiation therapy: its role in ovarian cancer.

PURPOSE: In spite of high initial response rates, many patients with epithelial ovarian carcinoma eventually fail their primary treatment. Further treatment with second-line regimens has been ineffective in producing durable responses. Thus, whole abdomen radiation therapy was evaluated as a salvage therapeutic modality as to its feasibility, efficacy, and toxicity. METHODS AND MATERIALS: Between June 1983 and June 1990, 44 patients who failed one or more chemotherapeutic regimens were treated with whole abdomen radiation therapy. Forty patients had epithelial carcinoma of the ovary and the remaining had primary adenocarcinoma of the peritoneal cavity. Radiation was delivered with an open-field technique and 2500 cGy were planned to the whole abdomen, with a boost when indicated. Prior to radiation, the amount of residual disease after debulking was noted to be microscopic in one-half of the patients and macroscopic in the other half. Pelvis alone was the site of residual disease in 14 patients, and upper abdominal involvement was found in 30. RESULTS: Five patients (11%) were unable to complete the planned therapy secondary to acute toxicity. The 4-year actuarial survival and recurrence-free survival rates for the entire group were 23% and 22%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease at 37% and 42% were significantly better than those for the patients with macroscopic residual disease at 9% and 5% (p < 0.005; p < 0.001) at 4 years, respectively. Patients with disease limited to pelvis only had a recurrence-free survival of 56% compared to 0% when the upper abdomen was involved (p < 0.005). The abdomino-pelvic cavity was the first site of recurrence in 28 of 31 patients in whom the site of recurrence could be determined. Eight patients (18%) experienced bowel complications, of whom five needed surgical intervention. CONCLUSIONS: Whole abdomen radiation therapy with a pelvic boost is feasible with acceptable acute and late toxicity. It is effective in patients with minimal residual disease.

Results of radiotherapeutic management of primary carcinoma of the vagina.

Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina.

Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection?

OBJECTIVE: To compare the pain associated with ceftriaxone sodium injections by using two different diluents, ie, lidocaine hydrochloride and sterile water. DESIGN: Prospective study of adolescents who were culture positive for gonorrhea. Random selection of the diluent used for the intramuscular ceftriaxone therapy. SETTING: Urban, hospital-based adolescent medicine service. SUBJECTS: Thirty-nine adolescents and young adults, predominantly of black or Hispanic backgrounds, ranging in age between 14 and 23 years (mean age, 17.6 years; median age, 17 years), of whom 27 were females. METHODS: Pain predictions were elicited from the adolescents before treatment. Pain ratings were obtained at five time intervals after the injections. All ratings were obtained by using a visual analog scale. RESULTS: No pain prediction differences before the injection were noted between the two groups. Individual t tests showed significant pain differences between the two groups at the time after the injection and at 10- and 20-minute and 6-hour intervals. Repeated-measures analysis of variance models showed that the diluent effect on pain was significant. CONCLUSION: Lidocaine can reduce the amount of pain of an intramuscular injection of ceftriaxone when compared with sterile water as a diluent. These findings have implications not only for the treatment of gonorrhea but also for other situations where intramuscular injections utilizing a diluent may be necessary.

Radiation therapy in the management of gestational choriocarcinoma metastatic to the central nervous system.

The Albert Mathieu Chorionepithelioma Registry's 1800 cases were screened, and 70 cases of trophoblastic disease involving the central nervous system were abstracted. In addition, eight patients with central nervous system trophoblastic disease from the Western Trophoblastic Disease Center, Department of Obstetrics and Gynecology, University of Southern California (USC) Medical Center, were reviewed. Eighteen patients received chemotherapy and whole-brain irradiation, 25 were treated with chemotherapy alone, and 35 received neither chemotherapy nor irradiation. In the no-treatment group (in which most patients died before therapy was begun), there were no survivors, and 74% of the deaths resulted from central nervous system causes. In the chemotherapy-alone group, 24% survived and 58% died of central nervous system causes. In the chemotherapy and irradiation group, 50% survived but none of the deaths were due to central nervous system involvement. This study suggests that radiation has a distinct therapeutic role in the treatment of central nervous system choriocarcinoma, and provides evidence that the irradiated brain tends to resist recurrent disease even in those patients for whom the outcome is fatal.

Phase I trial of cisplatin and razoxane (ICRF-159) (NSC #119875) in advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Pilot Study.

Both cisplatin and razoxane have shown activity in squamous carcinoma of the cervix. Cisplatin at a dose of 50 mg/m2 intravenously every 21 days was combined with razoxane at two dose levels--750 mg/m2 weekly and 1150 mg/m2 weekly. Three patients were treated at the first dose level and six patients were treated at the second dose level of razoxane. No objective regressions were observed, and three patients refused to continue therapy at the higher dose of razoxane because of nausea and vomiting. Further study of this regimen in cervical cancer is not recommended.

The early historical roots of pediatric and adolescent gynecology.

BACKGROUND: The science of medicine is a constantly evolving process that builds on the experiences and observations of the past. We hypothesized that the issues of pediatric and adolescent gynecology were also of concern to physicians practicing in the 19th century. We sought to determine the extent to which our forebears of over 100 years ago considered, diagnosed, and treated these problems. METHODS: We conducted an exhaustive search through two English-language medical journals, The Obstetrical Journal of Great Britain and Ireland (vol. 1-7, 1873-1880) and The American Journal of Obstetrics (vol. 1-32, 1869-1895), for articles relating to pediatric and adolescent gynecology. RESULTS: The most frequently encountered subject was the surgical management of congenital absence or atresia of the vagina and associated anomalies of adjacent organs. By 1881, the opinion expressed by many investigators was that the method used by Thomas Addis Emmet to create an artificial vagina between the bladder and the rectum by a single-stage procedure of blunt dissection and the immediate placement of a glass vaginal dilator gave the best chance of a favorable outcome. The practice of making an artificial opening through the rectum was abandoned. In 1882, a review of published reports noted 43% postoperative mortality in children treated for benign and malignant ovarian tumors. A review article in 1891 reported a 10% mortality rate associated with treatment of the imperforate hymen. A research article in 1870 noted the mean age at menarche in England to be 14.96 years. Additional subjects in the literature included: "Acquired Venereal Disease in Children" warning of the need for "rigid ... scrutiny of the attendants and playmates of children" (1893), the enigmatic occurrence of "Vaginal Hemorrhage in an Infant Five-Days-Old" (1874), the brutal atrocities perpetrated against "The Child Wives of India" (1895), "Early Pregnancy" reviewing childbirth by young adolescents (1874), "Hermaphrodism" (1886), "The ... Hymen and Its Remains ..." (1871), a "Case of Fatal Hemorrhage from the Genital Organs" in which a 17-year-old exsanguinated from a vaginal laceration (1879), and "Primary Sarcoma of the Vagina ... in a Child Three-Years-Old" (1881). CONCLUSION: Modern pediatric and adolescent gynecology can trace its roots to well over a century ago.

Salvage mitomycin/5-fluorouracil after platinum-based therapy for women with advanced ovarian cancer and related gynecologic malignancies.

PURPOSE: to determine response rates, survival, and toxicity of a regimen of mitomycin-C and 5-fluorouracil in patients previously treated with platinum-based combinations for ovarian cancer and related gynecologic malignancies. PATIENTS AND METHODS: retrospective chart review of all cases of persistent or recurrent ovarian, fallopian tube, and peritoneal carcinoma treated with mitomycin-C 7 mg/m2 followed by continuous infusion of 5-fluorouracil 600 mg/m2/day over 4 days. RESULTS: 26 patients were treated after a median of 2 prior platinum-based regimens, 22 with ovarian cancer, 3 with peritoneal cancer, and one with fallopian tube cancer. Only 2 patients completed 6 or more cycles. 2 patients had partial responses (8%); no complete responses were seen. 24 patients died a median of 3 months after the initiation of therapy, while 2 patients were alive 4 and 8 months after beginning therapy. All deaths were attributable to disease, not complications of treatment. 8 patients required dose modification or treatment delay for toxicity. Nine patients required a total of 11 unscheduled admissions. CONCLUSIONS: toxicity attributable to mitomycin-C/5-fluorouracil therapy of ovarian cancer is acceptable, but responses are few. More effective alternative should be sought.

A bleomycin/ifosfamide/cisplatin regimen exhibits poor activity against persistent or recurrent squamous gynecologic cancers.

Persistent or recurrent squamous malignancies of the female genital tract are usually incurable by conventional therapy, and results of single agent chemotherapy have been disappointing. We undertook this study to confirm a previously reported response rate of 69%, using a regimen of bleomycin 30U, ifosfamide 5g/m2 with mesna 6g/m2, and cisplatin 50 mg/m2 (BIP) for recurrent cervical cancer. This regimen was used to treat persistent or recurrent squamous cancers in women with cervical cancer (n = 11), vaginal cancer (n = 1) and vulvar cancer (n = 1). Results were reviewed retrospectively and toxicities graded according to the criteria of the Gynecologic Oncology Group. No complete responses were seen. One patient had a partial response (10%, 95% confidence interval 0-28%). Five patients (50%), exhibiting stable disease during therapy with BIP, progressed after cessation of therapy. Of 9 women with symptoms after one cycle. Significant toxicities included neutropenic fever (3 grade 3, 3 grade 4), emesis (1 grade 3), confusion (2 grade 4), vaginal bleeding (2 grade 3), and renal failure (1 grade 3). Eight patients were transfused with a total of 28 units of red cells. After 23 months of follow-up, all patients were dead of disease. Mean survival was 10 months. Toxicity associated with this regimen can be significant, and results appear no better than those reported with single agent therapy.

The maternity home for adolescents: a concept from the past fulfilling a contemporary need.

Maternity homes endure as an important means of imparting total care to some of today's homeless pregnant girls. This description of one such program is intended to serve as a model for the modern maternity residence for teens. Homelessness is a major complication of adolescent pregnancy. We believe that a supervised group home can be utilized to provide comprehensive care for homeless pregnant young women. We compiled data over the past six years (1986-91) from a residential facility for pregnant teenagers and their newborns, where the principal coauthor serves as voluntary medical director. During this period, 285 homeless adolescent females were admitted to the facility; their average age was 15.75 years, and 50% were white, 37% were African-American, and 13% were latino. All of the residents who were assigned private bedrooms, received prenatal care, accredited on-site schooling, family-life education, social services, dietary counseling, day-care services, and meals. The average length of stay was four months. The average birth weight was 6.62 pounds. Sixteen percent of the newborns were placed for adoption. Data from 1987 through 1989 showed that 74% of the girls had either attained their educational or vocational objectives or were pursuing those goals at the time of discharge. Achievements included high school graduation, job training, and college attendance. We conclude that this type of residential environment provides a wide range of resources beneficial to the homeless pregnant teen and her baby.

Smoking, obesity, and survival in squamous cell carcinoma of the vulva.

One hundred thirty-six patients with invasive squamous cell carcinoma of the vulva were studied retrospectively to determine prognostic factors for survival. In the regression analysis, three variables were statistically significantly related to survival: smoking history, tumor size, and node status. Smokers had a 6.3 times greater risk than nonsmokers, node positivity imparted an 8.3 times greater risk than node negativity, and for each 1-cm increase in the size of the tumor, the risk of death increased by 46%. A relative decrease in survival in smokers was observed, despite a younger age and fewer positive nodes at diagnosis compared to nonsmokers. Increased surveillance in these patients may be warranted.