John P. Curtin

Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.

PURPOSE To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.

Cervical cancer in pregnancy : reporting on planned delay in therapy

Objective:To report our experience with invasive carcinoma of the cervix during pregnancy, assessing maternal morbidity due to treatment delay and reporting maternal and fetal outcome.Methods:Twenty-seven patients with invasive cervical cancer, who were pregnant at the time of diagnosis or treatment

Paget's disease of the vulva

Abstract Thirty-six patients with Pagets disease of the vulva were reviewed. Median age of the patients at diagnosis was 64 years (range 41–84 years). Five patients (14%) had an associated invasive adenocarcinoma of the vulva at the time of diagnosis. Of 31 patients with superficial noninvasive Pagets disease, 28 were available for follow-up. Treatment of patients with superficial Pagets disease was surgical and based on the extent of disease. Procedures performed included total vulvectomy (25), wide local excision (4), and skinning vulvectomy with skin graft (1). The median follow-up was 108 months (range 6–266 months). Twenty-two of twenty-eight patients remained free of disease. Six patients have required multiple procedures for recurrent superficial Pagets disease. Treatment of Pagets disease of the vulva is surgical. Radical surgery is the preferred treatment of patients with an associated invasive adenocarcinoma; three of five patients with an invasive adenocarcinoma were long-term survivors. Patients with superficial Pagets disease of the vulva should be treated by local excision utilizing frozen-section margin evaluation as a guide to extent of excision. Only one patient with an initial diagnosis of superficial Pagets disease of the vulva developed invasive adenocarcinoma.

Laparotomy to complete staging of presumed early ovarian cancer

Objective To assess the findings and complications laparotomies for completely staging presumed early-stage ovarian cancer in patients whose initial surgery was inadequate. Methods Records of 45 patients surgically restaged at our institution, after having been incompletely staged elsewhere, were reviewed for original operative, reports, pathologic diagnoses, restaging procedures, operative results, and perioperative complications. Results Initial clinical staging was IA, 28; IB, three; IC 12; II A, one; IIB, one. Histologic distribution was as follows: invasive epithelial, 19 (42%); borderline epithelial, 16(36%); germ cell tumor, seven (16%); and stromal tumor, three (6%). Seven of the 45 patients (16%) had their disease reclassified to a more advanced stage. Of patients with borderline ovarian tumors, two initially staged as IA, were restaged to IB and IC, and one was restaged from IIB to IIIA. Three patients with invasive epithelial adenocarcinoma were reclassified to a higher stage: one, with a presumed stage IC, poorly differentiated adenocarcinoma, to IIB; and a third, with a IIA, poorly differentiated adenocarcinoma, to IIIC. A patient with granulosa cell tumor, initially staged as IC, was restaged to IIB; Fifteen patients (33%) had complications after restaging laparotomy for presumed early ovarian cancer were reclassified to a higher stage, resulting in alteration of treatment for only one patient. In 18 patients with invasive cancer, the second operation confirmed the presence of low-risk stage IA/B disease, allowing adjuvant chemotherapy to be withheld. Conclusion Although restaging laparotomies provide important prognostic information with minimal morbidity, they provide little benefit to those patients already requiring chemotherapy based on the original operative findings.

Management of vulvar melanoma

Considerable debate centers on the optimal treatment for vulvar melanoma, as well as those clinicopathological factors influencing prognosis. We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990. Primary tumors were assessed according to Chung (47 patients) and Breslow (65 patients) microstaging systems. Fifty-nine patients (76%) underwent radical vulvectomy, ten patients (13%) had a partial vulvectomy, and nine patients (12%) had a wide local excision. Fifty-six also underwent inguinal node dissection. Median follow-up was 193 months. Median survival was 63 months. Ten-year survival by Chung level was as follows: I 100%; II, 81%; III, 87%; IV, 11%; V, 33%. Ten-year survival by tumor thickness was as follows: 0.75 mm, 48%; 0.75-1.5 mm, 68%; 1.51-3.0 mm, 44%; greater than 3.0 mm, 22%. Increased depth of invasion was associated with increased incidence of inguinal node metastasis. Cox regression analysis demonstrated prognostic significance for tumor thickness (P less than 0.001), inguinal node metastasis (P less than 0.001), and older age at diagnosis (P less than 0.001). Radical vulvectomy did not seem to improve survival over less radical procedures. Based on this experience, we recommend radical local excision for patients with malignant melanoma of the vulva. Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection.

Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.

PURPOSE To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.

Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers

Abstract Objective: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). Methods and Materials: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28–72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12–15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. Results: With a median follow-up of 20 months (range 3–65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p Conclusion: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.

Second-look operation for epithelial ovarian cancer: Laparoscopy or laparotomy?

Objectives To compare the results, complications, and hospital charges associated with laparoscopy versus laparotomy in second-look operations for epithelial ovarian cancer. Methods We conducted a retrospective chart review of 109 patients with invasive epithelial ovarian cancer who underwent a second-look operation between July 1, 1992, and June 30, 1995. Results Thirty-one patients (28.4%) underwent laparoscopy, 70 patients (64.2%) underwent laparotomy, and eight patients (7.3%) underwent both procedures at the same operation. The majority of patients (60.6%) presented with stage IIIC disease. Persistent ovarian cancer was found in 65 of 109 (59.6%) patients, including 17 of 31 (54.8%) evaluated by laparoscopy, 43 of 70 (61.4%) by laparotomy, and five of eight (62.5%) by both procedures. Significantly lower mean blood loss was noted in patients undergoing laparoscopy (27 mL) compared with laparotomy (208 mL) (P < .01). In addition, the mean operating time for laparoscopy (129 minutes) was significantly shorter than that for laparotomy (153 minutes) (P < .01), and mean hospital stay was shorter for patients undergoing laparoscopy (1.6 days) compared with laparotomy (6.8 days) (P < .01). All intraoperative and immediate postoperative complications were noted in patients who underwent laparotomy. There was no difference in day of surgery charges between the two procedures; however, total hospital charges were significantly lower for patients undergoing laparoscopy (

Regression of uterine low-grade smooth-muscle tumors metastatic to the lung after oophorectomy

9448) compared with laparotomy (

Soft-tissue sarcoma of the vagina and vulva : a clinicopathologic study

17,969) (P < .01). With a median follow-up of 22.0 months, recurrence after negative second-look surgery was noted in four of 27 (14.8%) patients evaluated by laparotomy and two of 14 (14.3%) patients evaluated by laparoscopy. Conclusion Laparoscopy may be an acceptable alternative to second-look laparotomy for interval evaluation of epithelial ovarian cancer. Second-look laparoscopy probably results in less morbidity, shorter operating time, shorter hospital stay, and lower total hospital charges. These results require confirmation in a randomized clinical trial.