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Natalie Gould,
Michael W Sill,
Robert S Mannel,
P H Thaker, Paul Disilvestro,
Steve Waggoner,
S Diane Yamada,
Deborah K Armstrong,
Lari Wenzel,
Helen Huang,
Paula M Fracasso,
Joan L Walker
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ABSTRACT: To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.
Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m(2) on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.
Patients were treated with paclitaxel 175 mg/m(2) IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m(2) IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m(2) IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).
Paclitaxel at 175 mg/m(2) IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m(2) IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.
Gynecologic Oncology 12/2011; 125(1):54-8. · 3.89 Impact Factor
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ABSTRACT: It is often difficult to distinguish a benign pelvic mass from a malignancy and tools to help referring physician are needed. The purpose of this study was to validate the Risk of Ovarian Malignancy Algorithm in women presenting with a pelvic mass.
This was a prospective, multicenter, blinded clinical trial that included women who presented to a gynecologist, a family practitioner, an internist, or a general surgeon with an adnexal mass. Serum HE4 and CA 125 were determined preoperatively. A Risk of Ovarian Malignancy Algorithm score was calculated and classified patients into high-risk and low-risk groups for having a malignancy. The sensitivity, specificity, negative predictive value, and positive predictive value of the Risk of Ovarian Malignancy Algorithm were estimated.
A total of 472 patients were evaluated with 383 women diagnosed with benign disease and 89 women with a malignancy. The incidence of all cancers was 15% and 10% for ovarian cancer. In the postmenopausal group, a sensitivity of 92.3% and a specificity of 76.0% and for the premenopausal group the Risk of Ovarian Malignancy Algorithm had a sensitivity of 100% and specificity of 74.2% for detecting ovarian cancer. When considering all women together, the Risk of Ovarian Malignancy Algorithm had a sensitivity of 93.8%, a specificity of 74.9%, and a negative predictive value of 99.0%.
The use of the serum biomarkers HE4 and CA 125 with the Risk of Ovarian Malignancy Algorithm has a high sensitivity for the prediction of ovarian cancer in women with a pelvic mass. These findings support the use of the Risk of Ovarian Malignancy Algorithm as a tool for the triage of women with an adnexal mass to gynecologic oncologists.
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Obstetrics and Gynecology 08/2011; 118(2 Pt 1):280-8. · 4.73 Impact Factor
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The American surgeon 09/2009; 75(9):864-5. · 1.28 Impact Factor
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ABSTRACT: PURPOSE A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)-supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. PATIENTS AND METHODS Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m(2) as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). CONCLUSION In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.
Journal of Clinical Oncology 06/2009; 27(19):3104-8. · 18.37 Impact Factor
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ABSTRACT: To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with extended field irradiation in women with cervical cancer metastatic to the para-aortic nodes.
Patients with carcinoma of the cervix and histologically documented para-aortic node metastases were eligible for this phase I/II trial. Chemotherapy agents were administered weekly concurrent with extended field radiation with escalating doses of paclitaxel from 30-50 mg/m(2) in each of three cohorts of three patients each. A phase II cohort was then evaluated at the selected maximum tolerated dose (MTD).
The MTD was determined to be cisplatin 40 mg/m(2) (maximum dose of 70 mg) and paclitaxel 40 mg/m(2) administered weekly for six cycles concurrent with extended field radiation therapy. There were 19 evaluable patients for the phase II analysis of toxicity and efficacy. Grade three and four gastrointestinal toxicity was seen in 6 and neutropenia in 7. Radiation therapy was successfully completed in 36.8% of patients at eight weeks and in 68.4% of patients at nine weeks, with a median time to completion was 56 days. A total of 27 evaluable patients were enrolled, twelve are dead (mean survival of those deceased is 25 months), and 15 (56%) are alive, and have been followed for a mean of 48 months (range 25-68; median of 46 months).
Paclitaxel and cisplatin combination chemotherapy concurrent with extended field pelvic para-aortic irradiation can be administered at the described MTD and shows a higher than previously reported disease-free survival in relation to historical data. The 56% survival to date, and 50% estimated 48 month survival, warrants validation in a larger prospective cohort. Central radiation dose reduction is being considered in the next trial to decrease late toxicity of regimen.
Gynecologic Oncology 12/2008; 112(1):78-84. · 3.89 Impact Factor
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ABSTRACT: Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass.
Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC.
Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8-89.3).
An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.
Gynecologic Oncology 11/2008; 112(1):40-6. · 3.89 Impact Factor
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ABSTRACT: Sentinel lymph node (SLN) dissections have a high sensitivity and negative predictive value for the detection of metastatic disease. The objective of this study was to examine the inguinal recurrence rate along with complication rates for patients undergoing inguinal SLN dissection alone for vulvar carcinoma.
An IRB approved prospective study enrolled patients with biopsy proven squamous cell carcinoma of the vulva. Peritumoral injection of Tc-99 sulfur colloid and methylene blue dye was used to identify SLNs intraoperatively. Patients with SLNs negative for metastatic disease were followed clinically. Patients with metastasis detected in a SLN subsequently underwent a full groin node dissection followed by standard treatment protocols.
Thirty-six patients were enrolled onto study with 35 undergoing a SLN dissection. All SNL dissections were successful with a mean of 2 SLN obtained per groin. There were 24 patients with stage I disease, 8 stage II, 3 stage III and 1 stage IV. A total of 56 SLN dissections were performed with 4 patients found to have inguinal metastasis by SLN dissection. There were 31 patients with a total of 46 SLN dissections found to be negative for metastatic disease. The median follow-up has been 29 months (range 8 to 51) with 2 groin recurrences for a groin recurrence rate of 4.3% and a recurrence rate per patient of 6.4%. There have been no reports of groin breakdown, extremity cellulitis or lymphedema.
The recurrence rate for patients undergoing inguinal sentinel node dissection alone is low. These patients did not experience any complications as seen with complete groin node dissections. Sentinel lymph node dissection should be considered as an option for evaluation of inguinal nodes for metastatic disease.
Gynecologic Oncology 05/2008; 109(1):65-70. · 3.89 Impact Factor
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Richard G Moore,
Amy K Brown,
M Craig Miller,
Steven Skates,
W Jeffrey Allard,
Thorsten Verch,
Margaret Steinhoff,
Geralyn Messerlian, Paul DiSilvestro,
C O Granai,
Robert C Bast
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ABSTRACT: The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125.
Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP, HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and ERBB2 (Her2) and were compared to final pathology results. Logistic regression models were estimated for all markers and combinations, with cross-validation analysis performed to obtain the sensitivities at set specificities of 90%, 95%, and 98%.
Two hundred and fifty-nine patients with adnexal masses were enrolled. Of these, 233 patients were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all marker levels except Her2 differed significantly between patients with benign masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%). Comparatively, combined CA125 and HE4 yielded the highest sensitivity at 76.4% (specificity 95%), with additional markers adding minimally to the sensitivity of this combination. HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker.
As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4 is a more accurate predictor of malignancy than either alone.
Gynecologic Oncology 03/2008; 108(2):402-8. · 3.89 Impact Factor
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ABSTRACT: For women with early stage ovarian cancer (ESOC), comprehensive staging is the standard of care and studies suggest that these patients may not require further treatment. For women with incidentally diagnosed ovarian cancer there is a lack of consensus as to whether surgical staging be performed, particularly if chemotherapy is recommended.
We performed this retrospective study to determine the outcomes of women treated with chemotherapy for clinically apparent ESOC, stratified by whether staging was performed or not.
This study was approved by institutional review board. All patients presenting to the Multidisciplinary Gynecologic Oncology Tumor Board between 1998 and 2005 with a consensus opinion of having clinically apparent ESOC were identified. Staging (partial or complete) was determined by a study pathologist and patients were stratified as being staged or unstaged. Survival was estimated using the Kaplan-Meier method. STATA 8.0 was used for all calculations.
Eighty-eight patients were identified: 52 (59%) were staged and 36 (31%) were not. Median follow-up was 50 and 59.5 months, respectively. The majority of patients received carboplatin and paclitaxel in both cohorts with a median of 6 cycles. Five-year Disease Free Survival was 85% versus 80%, respectively (P = 0.54). Five-year Overall Survival was 85% versus 88% (P = 0.688).
For women presenting with a clinically apparent ESOC in whom chemotherapy is administered, there does not seem to be an additional benefit to surgical staging. A prospective trial of women with clinically apparent ESOC to test this hypothesis should be considered.
American journal of clinical oncology 03/2008; 31(1):39-42. · 2.21 Impact Factor
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Don S Dizon,
Sherry Weitzen,
Adam Rojan,
Joanna Schwartz,
Jane Miller, Paul Disilvestro,
Mary E Gordinier,
Richard Moore,
Trevor Tejada-Berges,
Leslie Pires,
Robert Legare,
Cornelius O Granai
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ABSTRACT: Although the standard of care for advanced epithelial ovarian cancer (EOC) is six cycles (6C) of platinum-taxane (PT), there have been no studies on the optimal duration of treatment in the era of adjuvant taxanes. At our center, some women receive eight cycles (8C) of PT, based on physician judgment. We were interested in evaluating the outcomes of women treated with 8C of PT for EOC as compared to a cohort who received 6C.
We retrospectively identified women with Stage III or IV EOC between 1998 and 2003 who received 6C or 8C of PT. The endpoints were disease-free (DFS) and overall survival (OS). CA-125 response was defined as a decrease in CA-125 of 50% in four serial samples or of 75% over three samples.
One hundred and twenty-two women met criteria for inclusion; 84 received 6C, and 38 received 8C. Comparing the cohorts receiving 6C versus 8C, 71% versus 26% were optimally debulked (P < 0.01). 79 patients were evaluable by CA-125 (52 6C/27 8C), and all responded. 88% receiving 6C and 81% receiving 8C normalized their CA-125 at end of treatment (P = 0.20). The proportion with a normal CA-125 at Cycle 2 was 29% versus 12%, respectively (P = 0.15) and, at Cycle 4, was 88% versus 36%, respectively (P < 0.01). DFS was 13 months with 6C and 8 months with 8C (P = 0.01). OS was 31 versus 23.5 months (P = 0.02), respectively. When the survival analysis is restricted to suboptimal debulked patients only, the DFS is 12.5 versus 8 months (P = 0.02), and OS is 32 versus 26.5 months (P = 0.15), respectively.
Two further cycles of PT did not improve DFS or OS for patients with advanced EOC. Patients who do not achieve remission after 6C are unlikely to benefit from additional chemotherapy using the same agents and should be considered for clinical trials involving novel agents with different mechanisms of action.
Gynecologic Oncology 03/2006; 100(2):417-21. · 3.89 Impact Factor
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ABSTRACT: With the use of steroid premedication, the incidence of severe hypersensitivity reactions (S-HSR) to paclitaxel is estimated to be 2%. For those who develop a S-HSR to paclitaxel, docetaxel has been employed as an alternative agent though the presence of cross-sensitivity has not been established. We sought to define the incidence of S-HSR to docetaxel following a paclitaxel S-HSR in an academic women's cancer program.
Patients treated with either paclitaxel (P) or docetaxel (D) between 11/1999 and 8/2004 were identified through our pharmacy database. Records were reviewed and data collected on those patients who had a S-HSR, defined as symptoms for which drug was discontinued, to P, D, or both.
718 patients received P and 93 received D. 59 received D following treatment with P. The presence of S-HSR for P was 2.2% (16/718 patients) and for D was 9.7% (9/93 patients). 10 patients with S-HSR to P crossed over to D and all nine patients reacting to D had a prior reaction to T for a cross-sensitivity rate of 90% (9/10 patients).
Cross-sensitivity of D after P was 90% at our institution. Given the different vehicles used in P and D, it is likely attributed to the taxane moiety. Caution is required with re-challenge of patients with docetaxel if they have previously reacted to paclitaxel.
Gynecologic Oncology 02/2006; 100(1):149-51. · 3.89 Impact Factor
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ABSTRACT: This study examined dose scheduling, safety, and efficacy of adapalene in the treatment of CIN2 and CIN3.
Patients were instructed on insertion and removal of an adapalene delivery system. Treatment regimens of 4, 8, and 14 days were utilized. Biopsies were performed on day 90 to assess efficacy. Safety was evaluated with toxicity questionnaires and patient interviews.
Two patients treated for 4 days had stable disease. Twenty-three patients treated for 8 days demonstrated an overall 61% (14 of 23) response rate. Twenty-four patients treated for 14 days had an overall 38% (9 of 24) response rate. No patient had disease progression. Compared to untreated historical controls, significantly improved efficacy was demonstrated for patients with CIN2. Patients with CIN3 had improved efficacy, though not statistically significant.
The lack of side effects and practicality of home use make adapalene a nontoxic and safe alternative to surgical therapy in patients with CIN2 and CIN3.
Journal of Lower Genital Tract Disease 02/2001; 5(1):33-7. · 1.07 Impact Factor
