A phase II trial of CI-958 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study

OBJECTIVES: To estimate the antitumor efficacy of CI-958 in patients with measurable recurrences of platinum-sensitive ovarian carcinoma and to determine the nature and degree of toxicity of CI-958 in these patients. METHODS: Patients received CI-958 560 mg/m2 intravenously every 3 weeks and tumor measurements were performed every one to two cycles. RESULTS: Of 23 patients entered in the study, there was one complete response and 10 patients had stable disease with short response durations. CONCLUSIONS: CI-958 has minimal activity in recurrent platinum-sensitive ovarian carcinoma at the dose and schedule tested.     

Analysis of clinical trials in gynecologic cancer—Timing and interpretation

When and how often a clinical trial is analyzed is as important as the use of appropriate methodology. Premature analysis may result in inaccurate estimation of tumor response and adverse effects as well as misrepresentation of survival. Moreover, bias may be introduced or the study may be abandoned entirely. Of parallel importance to the timing is the emphasis given to the analyses. If a randomized comparative trial of two regimens is conducted and a significant therapeutic effect is not discerned, the study is generally classified as a negative study. This view is oversimplified; the negative conclusion drawn must have a much more limited scope than is generally appreciated. Lastly, the pitfalls of interpreting time variable curves such as survival are of special note. Quite often the "tails" of the curves totally belie the true implications of the analysis.     

Physiologic profile of recreational male and female novice and experienced Tae Kwon Do practitioners

AIM: Subjects, 28 recreational male and female novice and experienced Tae Kwon Do practitioners (age 19-42 years), were examined on 6 physiological parameters: body composition (BF%, skinfold measures), flexibility (sit-and-reach and leg-splits tests), lower and upper-body dynamic muscular strength (leg press and bench press), abdominal strength and endurance (1-minute timed, bent-knee sit-ups test), lower extremity explosive power (vertical jump-and-reach test), and cardiovascular endurance (graded exercise treadmill test). METHODS: Subjects were assigned to 1 of the 4 following groups: Tae Kwon Do experienced and trained men (MT), Tae Kwon Do experienced and trained women (FT), novice Tae Kwon Do men (MN), and novice Tae Kwon Do women (FN). RESULTS: Results of multiple testing procedures and comparison across groups indicated that Tae Kwon Do black belts were more athletically fit as compared with that of novice Tae Kwon Do practitioners of the same sex in spite of the fact that male and female black belts were older than their novice counterparts. Experienced Tae Kwon Do subjects were stronger as measured by lower body strength and showed better aerobic performance capacity as well as lower percent body fat. Additionally, MT subjects demonstrated higher flexibility. CONCLUSION: The highly diverse training, repeated and continuous use of the legs and arms alone or combined with maximal stretching, and high intensity exercise may account for observed differences among groups.     

Rapid escalation of weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease: a Gynecologic Oncology Group study

Patients with postmolar nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the relationship of efficacy and toxicity to a rapidly escalating dose of weekly intramuscular methotrexate. The treatment was initiated at 40 mg/m2 weekly of intramuscular methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at 2-week intervals until a maximum dose of 50 mg/m2 per week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Forty-six of sixty-two (74%) evaluable patients had a complete response to this regimen. Duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. Eight patients experienced leukopenia at a median of 3200/microliters (range 2100-3900). Two patients had platelet nadirs of 128,500 and 131,000. Only 50% (8/16) of the nonresponders subsequently responded to second-line 5-day methotrexate every 2 weeks. Fifteen of the sixteen weekly intramuscular methotrexate failures ultimately had complete responses after treatment with subsequent chemotherapy. In this study, second-line therapy results support administration of another agent such as dactinomycin rather than 5-day methotrexate. This higher dose (1.36 relative dose intensity to median complete response) of weekly intramuscular methotrexate therapy (40 mg/m2) is no more effective and of similar toxicity to a lower-dose regimen (30 mg/m2) reported earlier.     

Long-term results of the Blom-Singer speech rehabilitation procedure

We report a 64% long-term success rate in our series of 66 patients who have undergone the tracheoesophageal puncture (TEP) procedure with follow-up ranging from one to 3 1/2 years. Poor motivation and compliance were the most common factors noted in patients who failed to obtain or maintain tracheoesophageal speech. Other problems causing failure were technical problems relating to the TEP and medical problems. The success rate in the last 24 cases of our series has improved to 83%. The "collared" prosthesis, more careful patient selection, and emphasis on a team approach seem to be important factors for the higher success rate. The Blom-Singer TEP procedure is a safe, simple, and effective means of alaryngeal communication for selected patients.     

A clinical and pathologic study of 30 cases of malignant mixed mullerian epithelial and mesenchymal ovarian tumors: A gynecologic oncology group study

Between November 1971 and June 1980, thirty patients with primary malignant mixed mullerian tumors of the ovary were entered into a Gynecologic Oncology Group registry and treatment protocol. The mean age of the patients is 60.4 years. Six were Stage II, twenty-three were Stage III, and one patient had Stage IV disease. Among the 30 cases, 15 were designated carcinosarcomas (CS) and 15 were mixed mesodermal sarcomas (MMS). Twenty-three of the thirty study patients died from 1 to 16 months following their initial surgery. Two of the seven living patients have persistent cancer at 11 and 54 months. Four patients were alive and well at 6, 11, 22, and 32 months at the close of the study. Of the 12 patients receiving vincristine, dactinomycin, and cyclophosphamide (VAC) with (8 cases) or without (4 cases) radiation therapy (RT), there were two clinical complete responses; both died with disease at 6 and 16 months. One of the six patients receiving adriamycin had a complete response (CR). She is alive with disease at 11 months. There was no apparent difference in the survival or stage distribution among the cases with CS and MMS. Survival was somewhat better for the patients with earlier stage disease or smaller residual tumor burden.     

Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study)

A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.     

A phase II evaluation of cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study

Cisplatin is one of the most active single agents in advanced squamous cell carcinoma of the cervix and is synergistic with 5-fluorouracil in the laboratory. The Gynecologic Oncology Group has conducted a phase II trial in which cisplatin at 50 mg/ml2 given intravenously on Day 1 was combined with 5-fluorouracil 1000 mg/m2 daily given as a 24-hr infusion on Days 1-5. Treatment was repeated every 21 days. Fifty-five patients were treated with this regimen, resulting in seven complete remissions (12.7%) and five partial remissions (9.1%). The median survival was 6.4 months. Toxic effects of grade 2 or greater were leukopenia in 10 patients (18.2%), thrombocytopenia in 2 patients (3.6%), gastrointestinal effects in 25 patients (45.5%), and renal effects in 1 patient (1.8%). On the basis of these results, the cisplatin and 5-fluorouracil regimen does not appear to have any advantage over cisplatin alone in advanced cervical cancer.     

Dactinomycin in the treatment of recurrent or persistent endometrial carcinoma: A Phase II study of the Gynecologic Oncology Group

OBJECTIVES: The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival for patients with disease not amenable to surgery or radiation therapy is poor. Dactinomycin has proven activity against a wide variety of solid tumors but has not been tested against endometrial cancer. Using pharmacokinetic data supporting an intermittent, single-dose schedule, this Phase II Gynecologic Oncology Group study was conducted to determine the antitumor activity and toxicity of dactinomycin in patients with persistent or recurrent endometrial adenocarcinoma. METHODS: Eligibility was limited to patients with measurable disease, adequate renal, hepatic, and bone marrow function, and no more than one prior chemotherapy regimen. Treatment consisted of 2 mg/m(2) slow intravenous push of dactinomycin over 15 min with courses repeated every 4 weeks. RESULTS: A total of 27 patients were entered in this study between April 1996 and September 1996; all were evaluable for toxicity and 25 were evaluable for response. Overall, 12/25 (48%) patients had received prior radiation therapy and all had received prior chemotherapy. Sites of measurable disease were pelvis (9 patients) and distant (16 patients). There was 1 complete response and 2 partial responses for an overall objective response rate of 12%. Aside from emesis (grade 3, 2 patients; grade 4, 2 patients) significant nonhematologic toxicity was rare. The most common toxicity was neutropenia (grade 3, 2 patients; grade 4, 10 patients). CONCLUSION: Toxicity was deemed acceptable but the limited effectiveness of dactinomycin precludes further clinical development in this patient population.     

Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group Study

From October 1995 to March 1997, a phase II trial of topotecan was carried out in chemotherapy-naive women with advanced, persistent, or recurrent uterine leiomyosarcomas. Thirty-six patients were entered. Median age was 53 years. Performance status was 0 (50%) in 18, 1 (36%) in 13, and 2 (14%) in 5. Most patients, 33 (92%), had undergone prior surgery, and 8 (22%) prior radiation therapy. Topotecan, 1.5 mg/m2. was administered intravenously daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. Patients received 1 to 13 courses with a median of 3 courses. The most frequent grade 4 adverse effects were neutropenia in 28 (78%), leukopenia in 8 (22%), thrombocytopenia in 3 (8%), and anemia in 3 (8%). Complete response was seen in 1 (3%), partial response in 3 (8%), stable disease in 12 (33%), and increasing tumor in 20 (56%). Thus topotecan at this dose and schedule does not appear to have major activity in uterine leiomyosarcomas.