A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.

BACKGROUND: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. PATIENTS AND METHODS: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. RESULTS: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. CONCLUSIONS: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. TRIAL REGISTRATION: Clinicaltrials.gov, NCT 01666444.

A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.

BACKGROUND: Two strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation. METHODS: A phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg(-1)) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg(-1)) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752. RESULTS: A total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles. CONCLUSIONS: Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed.

A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.

OBJECTIVES: Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family. PATIENTS AND METHODS: Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA). RESULTS: The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies. CONCLUSIONS: The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers.

Successful treatment of two patients with gestational trophoblastic neoplasm presenting with emergent neurologic symptoms.

The objective of this study is to present the successful treatment of two young patients with gestational trophoblastic neoplasms (GTN) presenting with emergent neurologic symptoms without any gynecological problems. Case 1, a 22-year-old patient, was admitted to an infectious disease ward, with admitting diagnosis of encephalitis due to neurologic symptoms. Case 2, a 33-year-old patient, underwent craniotomy due to hemorrhagic brain tumor in the neurosurgery department. The diagnosis of GTN should be considered in any woman of reproductive age who has neurologic symptoms. It seems that multiagent chemotherapy in conjunction with whole-brain irradiation results in acceptable survival rate in brain metastatic GTN patients. Craniotomy is often necessary in fulminant cases.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors.

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996-2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17-53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.

EMA-EP regimen, as firstline multiple agent chemotherapy in high-risk GTT patients (stage II-IV).

Multiple agent chemotherapy in high-risk metastatic gestational trophoblastic tumor patients is a problem for any medical team. In this study, EMA-EP chemotherapy (etoposide, methotrexate, actinomycin, and cisplatinum) was evaluated as firstline chemotherapy to manage high-risk GTT metastatic patients. Seventeen high-risk metastatic patients, including 14 without and 3 with brain metastasis, who were candidates to firstline multiple agent chemotherapy between April 2000 and March 2003 in Vali-e-Asr hospital took part in a prospective study under EMA-EP regimen. EMA-EP was prescribed in two periods: EMA in two consecutive days in week 1 and EP in 1 day in the following week with a week interval between these two (each cycle was repeated every 2 weeks). In brain metastasis group, patients got high-dose medication (methotrexate) together with brain radiotherapy. Remission, toxicity, full dose tolerance, and recurrences of patients were evaluated. Median age of patients was 30 (15-49), and they received 100 courses of chemotherapy including 75 low-dose courses and 25 high-dose courses. 71% of courses were done in full dosage (83% in low dose and 36% in high dose). The most common cause for dosage reduction was leukopenia. Two patients did not complete the regimen, one due to hypersensitivity and the other due to fever and leukopenia leading to death. All others, who received complete courses, achieved remission. In the group without brain metastasis, one case of recurrence was observed. Grade 3 anemia, grade 3 and 4 leukopenia, and grade 3 and 4 thrombocytopenia were observed in 3, 12, and 3% of patients, respectively. In current study, EMA-EP regimen in patients with high-risk metastatic GTN patients (with or without brain metastasis) lead to remission in all patients who completed the treatment courses.

Borderline ovarian tumours: clinical analysis of 38 cases.

Thirty-eight patients with ovarian tumours of low malignant potential (borderline) were diagnosed and treated in Tehran University Gynecology Oncology Department from 1991 to 2002, and have been reviewed. In this study age, clinical behavior, symptoms, surgical stage, type of tumour, surgery, adjuvant treatment, survival and recurrences were evaluated. A retrospective chart review was performed on these 38 patients who were treated for histopathologically confirmed tumours of low malignant potential between 1991-2002. The mean age was 34.4 years, range (14-83) (SD: 18.33). Post surgical FIGO staging was: Stage I=93.75%, stage III 6.25%. Histologic subtypes were: Serous 76.31% (29 patients), Mucinous 21.05% (8 patients), Mixed types 2.63% (1 patient). Mean pre-operative CA125 value was 114.90 (SD: +/- 90.30). Thirty-three percent of patients had only a simple cyst in ultrasonography. Conservative surgery was performed in 76.32% (29 patients). More radical surgery (TAH + BSO) was performed in 9 patients (23.68%). There were 6 recurrences. Three patients with recurrence and invasive implants received chemotherapy and secondary surgery was performed. Survival rate was 100% at 3 years for all stages and 89% at 5 years. One patient died of recurrent disease at 48 months after initial diagnosis. Our data suggest that LMP tumours are most frequently diagnosed in stage I. Most common histological type was serous, and 5 of the recurrences of (6 patients) were initially diagnosed at stage I, and had been treated with conservative surgery with no adjuvant therapy.

Simple hysterectomy in the presence of invasive cervical cancer in Iran.

The objective of this study was to determine the reasons leading to an inappropriate simple hysterectomy in the presence of invasive cervical cancer. During 1997-2001, 62 cases of invasive cervical carcinoma that had been treated by simple hysterectomy were referred to the gynecology oncology service in Vali-e-Asr hospital, Tehran, Iran. Five had microinvasive carcinoma. The remaining 57 women had either adenocarcinomas or squamous cell carcinoma (SCC). Medical records were reviewed retrospectively to determine the reasons for inappropriate hysterectomy. Reasons for inappropriate hysterectomy were as follow: lack of preoperative Pap smear (P/S) (29%), deliberate hysterectomy for biopsy-proven cancer (25.8%), negative P/S (6.5%), inadequate evaluation of abnormal P/S (6.5%), failure to perform an indicated conization (3.2%), and emergent operation because of uterine perforation (1.6%). Reasons for inappropriate hysterectomy in the remainder of patients (27.4%) were not found because of lack of sufficient information. Although 45.2% of these patients had complained for vaginal bleeding, only four of them had preoperative endocervical and endometrial sampling. Despite the increasing emphasis on performing cervical cancer screening before hysterectomy, only 18 (29%) referral patients had preoperative P/S. We conclude that by close adherence to the cervical cancer screening guidelines and appropriate evaluation of the presenting symptoms, we may avoid inappropriate management of cervical carcinomas with simple hysterectomy. Many cases of simple hysterectomy in the presence of biopsy-proven squamous cell carcinoma of the cervix necessitates some reconsideration of gynecology oncology postgraduate courses for general gynecologists.

Uterine papillary serous carcinoma after pelvic radiation therapy for cancer of the cervix.

The carcinogenic effect of ionising radiation in humans has well documented in both atomic bomb survivors and patients exposed to therapeutic radiation. Patients irradiated for cancer of cervix have frequently been studied for the later development of secondary malignancies because treatment is relatively successful and many patients survive long enough to be at risk for late complications of radiotherapy. Most investigations have revealed an increased incidence of uterine sarcoma following pelvic radiation therapy for a variety of gynecologic disorders (Norris and Taylor, 1965; Fehr and Prem, 1974). Wagoner, in a review of over 1800 women treated with ionising radiation for invasive cervical cancer, reported a fourfold increase in risk for the later development of uterine sarcoma (Wagoner, 1984). In this paper we report the case of uterine papillary serous carcinoma 16 years after pelvic X-ray therapy for cervical cancer.

BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study.

OBJECTIVE: The aims of this study were to determine the frequency of BRCA1 gene alterations in an unselected, clinic-based series of ovarian cancer cases; to evaluate the usefulness of family history in predicting the likelihood of a disease-causing mutation; and to document the occurrence of polymorphic variants in BRCA1 and to determine their distribution among families accordingly to history of breast and/or ovarian cancer. METHOD: Two hundred fifty-eight women with primary epithelial ovarian cancer, entered onto a nonclinical protocol of the Gynecologic Oncology Group, were analyzed for BRCA1 germline alterations by single-strand conformation polymorphism analysis. RESULTS: Protein-truncating mutations in BRCA1 were identified in 12 patients (4.6%). The median age of cancer diagnosis in BRCA1 mutation carriers was 47 years compared to 57 years in patients without mutations (P = 0.02). All but 1 of the patients with BRCA1 mutations reported a family history of breast and/or ovarian cancer and 8 had a first-degree relative with cancer. Twelve mutations of unknown significance were also identified. An association was also noted between the presence of common polymorphisms in BRCA1 and family history of cancer. Polymorphisms were present at higher frequency among women without a family history of cancer compared to women with positive family histories, suggesting they are associated with reduced risk. CONCLUSION: In a clinic-based series of ovarian cancer patients, germline BRCA1 mutations were detected in 12 of 258 (4.6%) patients. A strong correlation was noted between the presence of mutations and family history of breast and/or ovarian cancer, indicating that these women are most likely to benefit from genetic susceptibility testing.

Oral topotecan as single-agent second-line chemotherapy in patients with advanced ovarian cancer.

PURPOSE: To evaluate oral topotecan as single-agent, second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen. PATIENTS AND METHODS: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days. Eligibility criteria included histologic diagnosis of International Federation of Gynecology and Obstetrics stage III or IV epithelial ovarian cancer, bidimensionally measurable disease, prior platinum-containing chemotherapy, age > or = 18 years, performance status < or = 2, and life expectancy > or = 12 weeks. RESULTS: Overall response rate was 21.6% (25 of 116 patients). Median duration of response was 25.0 weeks; median time to response was 8.4 weeks. Median time to progression was 14.1 weeks; median survival was 62.2 weeks. Grade 4 neutropenia was experienced by 50.4% of patients in 13.4% of courses administered. Grade 4 thrombocytopenia was experienced by 22.1% of patients in 5.1% of courses. Grade 3 or 4 anemia was experienced by 29.2% of patients in 8.5% of courses. Most frequent nonhematologic toxicities were predominantly (> 90%) grade 1 or 2 and included nausea, alopecia, diarrhea, and vomiting. CONCLUSION: Second-line oral topotecan administered at 2.3 mg/m2 for 5 days every 21 days demonstrated activity in patients with progressive or recurrent ovarian cancer after first-line platinum-based chemotherapy. This activity was comparable to that seen in previous studies with intravenous topotecan. Grade 4 neutropenia was less frequent with oral topotecan than previously reported for intravenous topotecan. Oral topotecan is an active, tolerable, and convenient formulation of an established agent for the second-line treatment of advanced epithelial ovarian cancer and may also facilitate exploring prolonged treatment schedules.

To peritonealise or not to peritonealise? A randomised trial at abdominal hysterectomy in Iran.

We conducted a trial to determine whether non-closure of the visceral and parietal peritoneum alters the intraoperative or post-operative course at abdominal hysterectomy. This was a parallel-group double-blind randomised controlled trial was performed on 66 women who underwent abdominal hysterectomy with or without salpingo-oophorectomy. Twenty-seven were allocated to the control 'closed' group and 39 women to the study 'open' group. The main outcome measures were operative time, estimated blood loss, postoperative pain assessed by visual analogue scale and amount of postoperative analgesia. The study was conducted in the Department of Gynecological Oncology in a university teaching hospital. The operative time was shorter (P < 0.05) and the time to ambulation without assistance was significantly shorter in study group. There were no difference in postoperative pain, blood loss, amount of postoperative analgesia and antibiotics in the two groups. Peritoneal closure at abdominal hysterectomy provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anaesthesia exposure. We suggest that the traditional practice of visceral and parietal closure be abolished at abdominal hysterectomy.

Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group.

PURPOSE: The activity and toxicity of topotecan were evaluated in a multicenter Phase II study for patients with previously treated squamous cell carcinoma of the uterine cervix. PATIENTS AND METHODS: Histologic confirmation of the primary diagnosis was required, as well as adequate performance status and vital organ function and the presence of measurable disease. Patients were allowed one prior regimen of systemic therapy, usually platinum-based. A two-stage accrual design was utilized with early stopping criteria and monitoring of toxicity. Topotecan was administered at 1.5 mg/m(2) per day for 5 consecutive days on a 21-day cycle with modifications based on hematologic toxicity. RESULTS: Forty-five patients were entered. Two patients were ineligible (incorrect tumor type) and 2 were inevaluable (never received therapy). One additional patient was not evaluable for response (nonmeasurable disease). A median of 2 cycles was administered to each patient (range: 1-17 cycles) with grade 4 neutropenia in 68% and grade 4 thrombocytopenia in 39% of patients, but without treatment-related deaths. Nonhematologic toxicity was generally mild and not dose-limiting. The overall (complete and partial) response rate among evaluable patients with measurable disease was 12.5% with stable disease in an additional 37. 5%. Median progression-free survival was 2.1 months. CONCLUSIONS: As a single agent topotecan shows modest antitumor activity, with manageable hematologic and nonhematologic toxicity, in patients with previously treated squamous cell carcinoma of the cervix. Further evaluation in chemotherapy-naive patients or in combination with cisplatin and/or radiation may be indicated.

Phase II evaluation of 24-h continuous infusion topotecan in recurrent, potentially platinum-sensitive ovarian cancer: A Gynecologic Oncology Group study.

OBJECTIVES: The aim of this study was to develop an alternative effective and more convenient administration schedule for intravenous topotecan when used as palliative treatment in ovarian cancer. METHODS: The Gynecologic Oncology Group conducted a Phase II trial of 24-h infusional topotecan (8.5 mg/m(2)) with treatment repeated every 3 weeks in 29 patients with platinum-sensitive recurrent ovarian cancer (prior response to platinum-based chemotherapy with a minimum treatment-free interval >/=6 months). RESULTS: The major toxicities of therapy were grade 4 neutropenia and thrombocytopenia which developed in 86 and 14% of patients, respectively. Other severe side effects were uncommon. Only 2 partial responses (7%) were observed in the 28 patients evaluable for response. CONCLUSIONS: Despite the relatively favorable ovarian cancer patient population treated in this trial (platinum-sensitive recurrent disease), the response rate was disappointingly low. Considering the three- to fivefold higher objective response rates observed in other trials employing topotecan in individuals with platinum-sensitive ovarian cancer utilizing a 5-day treatment program (delivered every 3 weeks), the results of the current study provide strong support for the conclusion that clinically relevant antineoplastic activity of this agent is highly schedule dependent.

Intraperitoneal alpha-interferon alternating with cisplatin in residual ovarian carcinoma: a phase II Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to study the combination of intraperitoneal alpha-interferon and cisplatin administered second-line in an alternating sequence in small volume residual epithelial ovarian cancer after second-look surgery and the activity of this combination based on prior response to first-line platinum compounds. METHODS: Sixty-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal alpha-interferon alternating with cisplatin given for eight cycles unless disease progression or unacceptable toxicity occurred. The patients were considered favorable if they were platinum-sensitive and/or relapsed 6 months or longer after completing treatment. Another reassessment laparotomy was performed within 12 weeks of completion of treatment in patients who were in clinical remission. RESULTS: Fifty-four patients were clinically evaluable and 18 were surgically reassessed, 5 of whom had a negative reassessment operation (20% complete response and 8% partial response). Of the 54 patients evaluable for toxicity, the most common adverse effects of more than grade 2 were gastrointestinal in 13 (47%), neutropenia in 9 (17%), and leukopenia in 6 (12%). Grade 4 toxicity was seen in 10 instances: 4 gastrointestinal, 2 neutropenia, 2 thrombocytopenia, 1 wound infection, and 1 allergic reaction. CONCLUSIONS: alpha-Interferon and cisplatin are active agents in favorable patients with minimal residual epithelial ovarian cancer at second-look. The combination of the two drugs administered in an alternating sequence appears to be associated with more side effects than when either drug is administered alone. The combination produced response rates similar to those seen when either drug is given alone.

Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.

PURPOSE: To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS: Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS: Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION: Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.

Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.

PURPOSE: This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors. PATIENTS AND METHODS: After tumor removal and thorough surgical staging, patients were enrolled on this study and treated with three courses of cisplatin, etoposide, and bleomycin (BEP). Reassessment laparotomy was required of consenting, appropriate patients initially, but became an optional procedure in 1989. RESULTS: Of 93 patients assessable on this trial, 89 are continuously free of germ cell cancer. At second-look laparotomy, two other patients were found to have small foci of immature teratoma; both remain clinically free of recurrence. One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93 patients are currently free of germ cell cancer. Follow-up duration ranges from 4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute toxicity was moderate. One patient developed acute myelomonocytic leukemia 22 months after diagnosis. Another patient was noted to have a malignant lymphoma 69 months after protocol treatment. CONCLUSION: Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients. The development of acute leukemia as a complication of treatment is disturbing and mandates careful long-term follow-up, but is unusual and does not alter the risk-to-benefit ratio of treatment.

A phase II trial of tricyclic nucleoside phosphate in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Study.

A Phase II trial of TCN-P was conducted in metastatic or recurrent squamous cell carcinoma of the cervix using a 5-day continuous infusion schedule. The starting dose was 35 mg/m2 x 5 days and courses were repeated every 6 weeks. Among 21 evaluable patients, 2 responses were observed. One patient had a complete response for 19+ months. Another patient had a partial response for 5+ months, but developed symptomatic hypocalcemia, requiring discontinuation of the drug. Using this dose and schedule TCN-P appears to have limited activity in metastatic or recurrent squamous cell cancer of the cervix.

Echinomycin (NSC 526417) in recurrent and metastatic nonsquamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group.

Eighteen evaluable patients with recurrent or metastatic nonsquamous carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. Seven patients had received prior chemotherapy. There was one complete response (5.6%), 95% confidence interval for response of 0-27%. The major toxicity was nausea and vomiting, which was moderate to severe in eight patients. Myelosuppression was minimal. Echinomycin in this dose and schedule displays minimal activity in patients with advanced nonsquamous carcinoma of the cervix.

Telephone counseling improves adherence to colposcopy among lower-income minority women.

PURPOSE: A randomized trial was conducted to evaluate the impact of a telephone counseling intervention to improve patient adherence to colposcopic examination for suspected cervical intraepithelial neoplasia (CIN). METHODS: Subjects were lower-income, minority women who missed a scheduled initial appointment for colposcopy at an urban medical clinic. Patients were randomly assigned to either a control condition (n = 42) or a telephone counseling condition (n = 48). The 15-minute, structured telephone counseling intervention protocol addressed educational, psychosocial, and practical barriers to colposcopy adherence. RESULTS: The most common patient-reported barriers to colposcopy adherence included a lack of understanding of the purpose of colposcopy (50%), worry about or fear of cancer (25%), and forgetting (23%). Telephone counseling was found to be highly effective in addressing these barriers and improving adherence to diagnostic follow-up and treatment. Of patients in the control condition, 43% complied with a rescheduled colposcopy appointment, compared with 67% in the telephone counseling condition. Logistic regression analysis indicated that the effect of telephone counseling was independent of sociodemographic confounder variables (odds ratio = 2.6; P less than .003). Additionally, 74% of patients who received the initial telephone counseling adhered to recommended treatment, compared with 53% of patients in the control condition. CONCLUSION: Brief, structured telephone contact may be a cost-effective mechanism for improving adherence to diagnostic follow-up and treatment for a variety of cancer screening tests.