Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: The primary objective of this study was to evaluate the safety and tolerability of a formulated IL-12 plasmid administered intraperitoneally (IP) in conjunction with intravenous (IV) carboplatin/docetaxel in platinum-sensitive ovarian cancer patients. METHODS: Escalating doses of IL-12 plasmid (phIL-12) formulated with the lipopolymer PEG-PEI-Cholesterol (PPC) were administered IP every 10-11 days for a total of four treatments and the highest dose was expanded to eight treatments. Patients also received IV carboplatin (AUC 5) and docetaxel (75 mg/m(2)) every 21 days. Patients were followed for safety, biological activity and antitumor activity after phIL-12/PPC treatment. RESULTS: All 13 patients enrolled in the study received both phIL-12/PPC and chemotherapy treatment. There were 49 plasmid-associated adverse events (AEs). The most common AEs were abdominal pain, transient hypotension, low grade fever, catheter site pain, chills, dysgeusia, infusion-related reaction, and nausea. These AEs appeared to be plasmid dose related. Grade 3 AEs included manageable abdominal pain and cytokine release syndrome. There were no dose limiting toxicities and the plasmid treatment did not augment the chemotherapy-associated AEs. The best overall antitumor response (17% CR, 33% PR, 42% SD and 8% PD) was typical of the patient population enrolled for the study. Translational studies showed rise in IFN-γ and TNF-α concentrations in a dose dependent manner. CONCLUSIONS: The escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well tolerated and did not appear to exacerbate the side effects or attenuate the efficacy of the chemotherapy treatment.

Surgically (laparotomy/laparoscopy) guided placement of high dose rate interstitial irradiation catheters (LG-HDRT): technique and outcome.

OBJECTIVE: To describe and evaluate the technique and the clinical outcome of a new modality for the treatment of women with persistent or recurrent pelvic malignancies utilizing surgically (laparotomy or laparoscopic) guided high dose rate (HDR) catheters to complete high dose rate interstitial irradiation therapy (LG-HDRT). METHODS: Between 6/2000 and 6/2004, 14 women with histologic evidence of postradiation persistent (3 patients) or recurrent (11 patients) pelvic disease underwent LG-HDRT. Five patients (36%) received treatment for a 2nd, 3rd or 4th recurrence. Preoperative clinical and radiologic evaluation to exclude evidence of extrapelvic disease was routine. Initial intraoperative evaluation included intraabdominal inspection and or biopsy to determine the extent of disease. A two "team" approach was used to place the 100 cm Teflon after loading HDR catheters. Each catheter had its open ends closed with bone wax prior to placement. Using a 14 gauge intravenous catheter as a guide, each HDR catheter was individually placed transvaginally. The tumor bed (treatment volume) was marked circumferentially with clips to facilitate treatment planning. Dosimetry was typically completed on the day of surgery and HDR therapy was started within the initial 24 postoperative hours. The catheters were removed transvaginally, without anesthesia following completion of therapy. RESULTS: Mean patient age was 63.1 years and weight was 138.2 lb. Squamous cell cancer of the vagina or cervix was the most common (64%) diagnosis. The mean time from initial diagnosis to LG-HDRT was 67.9 months. The procedure was completed laparoscopically in 71% of patients, with 4 patients requiring laparotomy (3 conversions from laparoscopy). The mean duration of surgery was 94.9 min and the mean hospital stay was 4.8 days. Only 2 patients (14%) were discharged prior to the completion of therapy. The mean number of catheters placed was 6.1 and the mean dose delivered was 20 Gy over a mean of 5 fractions. There were no major intraoperative complications. Postradiation complications were limited to DVT (1), bladder bleeding (1),

Poly(L-lactide/glycolide) suture: the effect of acute radiation.

UNLABELLED: The physical properties of Poly(L-lactide/glycolide) indicate that the suture retains approximately 80% of its original strength at 3 months and 60% of its original strength at 6 months. This new long-term synthetic absorbable suture offers postoperative fascial strength for an extended period when compared to other available absorbables. Importantly, many women with gynecologic cancer will undergo radiation therapy during this interval. This report is intended to evaluate the effects of ionizing radiation on this suture. METHODS: One lot (op strands) of size 1 PLG suture was used. Ten (10) strands were used for baseline study of out of package tensile strength. Eighty (80) strands were placed in a buffer solution (pH approximately 9.0) and incubated in an in vitro water bath approximately 48 h at 55 degrees C to simulate 4 weeks in vitro residence time. Following this in vitro hydrolysis 20 strands were tested. Sixty strands were placed beneath a piece of fresh full thickness porcine skin and subcutaneous tissue and exposed to 3, 30, and 70 Gy. All samples were evaluated for breaking strength and elongation-at-break using an Instron tensiometer. RESULTS: Analysis of variance performed at the different exposure level revealed no significant effect on tensile properties (p>0.1). CONCLUSION: The tensile properties of PLG suture are not adversely affected by ionizing radiation. This long-term absorbable suture is an alternative for fascial closure when extended periods of support are necessary in patients destined to receive therapeutic ionizing radiation.

Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy.

OBJECTIVE: The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging. METHODS: Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology. RESULTS: Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717). CONCLUSION: Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

Conservative management of stage I endometrial carcinoma after surgical staging.

OBJECTIVE: The aim of this study was to determine the outcomes of Stage I endometrial carcinoma patients who are managed without adjuvant radiation after comprehensive surgical staging. METHODS: A computerized hospital database identified women diagnosed with adenocarcinoma of the endometrium from 1993 to 1998. A chart review identified 864 women as having primary surgery for adenocarcinoma of the endometrium. A total of 670 of 864 patients (78%) underwent comprehensive surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal cytology. After 57 patients with high-risk histologic subtypes were excluded, 613 patients remained for analysis. RESULTS: A total of 321 of 325 Stage IB patients (99%) did not receive adjuvant radiation. Fifteen of 321 patients (5%) recurred; 9 recurred in the pelvis or vagina. All 9 local recurrences were salvaged with whole pelvic radiation (XRT) and brachytherapy (BT). Seventy-seven patients were diagnosed with Stage IC disease; 53 (69%) received no adjuvant therapy. Four patients (8%) recurred, of which 2 recurred in the vagina. Three of 4 patients (75%) were salvaged, 2 with XRT/BT and 1 with surgery and chemotherapy. For all Stage I patients, the 5-year disease-free survival was 93% and the 5-year overall survival was 98%. CONCLUSIONS: Surgically staged patients with endometrial carcinoma confined to the uterine corpus have a small risk of recurrence and the majority of these recurrences can be salvaged with radiation therapy. Conservative management of Stage I endometrial carcinoma patients is an effective treatment strategy.