Amy D Tiersten, M.D.

CA-125 surveillance for women with ovarian, fallopian tube or primary peritoneal cancers: What do survivors think?
Boyd, L.; Bedell, S.; Curtin, J.; Wallach, R.; Pothuri, B.; Muggia, F.; Tiersten, A.; Blank, S.
2011 MAR ;121(1):S64-S64, Gynecologic oncology
— id: 132764, year: 2011, vol: 121, page: S64, stat: Journal Article,

Phase II Evaluation of Liposomal Doxorubicin with Docetaxel in Patients with Metastatic Breast Cancer
Fasano, J; Hershman, D; Novik, Y; Levinson, B; Blozie, K; Tiersten, AD
2010 MAR ;5(1):17-21, Breast care
Background: Taxanes are effective in treating metastatic breast cancer. Liposomal doxorubicin (LD) is as effective as doxorubicin but less toxic. Patients and Methods: This phase II trial assessed the combination of LD and docetaxel (D). Between 12/2002 and 9/2005, 12 women received monthly LD (30 mg/m(2)) and weekly D (30 mg/m(2)). Cycles were continued until progression or toxicity. Primary outcome was time to progression. Secondary endpoints included response rate, time to treatment failure, duration of response, survival, and toxicity. Results: Median age was 49 (31-60) years. 9 (75%) patients had estrogen receptor-positive or progesterone receptor-positive tumors. 5 (41.7%) women had her-2/neu-positive tumors. 4 women stopped participation due to toxicity, and 7 due to progression. 8 (67%) participants (95% confidence interval (CI) 51.6-94.5%) had a partial response, and 2 (16.7%) had stable disease. Median time to progression was 9.6 months (95% CI 4.712.2). Median time to treatment failure was 6.5 months (95% CI 4.4-10.5). Median survival was 22.1 months (95% CI 9.640.8). Median duration of partial response was 2.7 months (95% CI 2.4-10.5). 10 (83%) women experienced grade 3/4 toxicities: neutropenia 3 (25%), infection 3 (25%), stomatitis 5 (41.7%), nausea 2 (16.7%), vomiting 1 (8.3%), dyspnea 2 (16.7%), pericardial effusion 1 (8.3), and palmar-plantar erythrodysesthesia 1 (8.3%). Conclusions: LD and D resulted in an encouraging response and unacceptable toxicities
— id: 108319, year: 2010, vol: 5, page: 17, stat: Journal Article,

Weekly Paclitaxel with intermittent imatinib mesylate (gleevec(r)>): tolerance and activity in recurrent epithelial ovarian cancer
Safra, Tamar; Andreopoulou, Eleni; Levinson, Benjamin; Borgato, Lucia; Pothuri, Bhavana; Blank, Stephanie; Tiersten, Amy; Boyd, Leslie; Curtin, John; Muggia, Franco
2010 Sep;30(9):3243-3247, Anticancer research
OBJECTIVE: Imatinib mesylate (IM, Gleevec), a potent PDGF/PDGFR tyrosine kinase inhibitor, affects stroma and vascular endothelial cells. Our study sought to determine the safety and activity of paclitaxel with an intermittent schedule of IM. MATERIALS AND METHODS: rEOC patients previously treated with platinum/paclitaxel and </=2 regimens for recurrence were enrolled. Paclitaxel 80 mg/m(2) was given on days 3, 10, 17 every 28 days and oral IM 300 mg bid on days 1-4, 8-11, and 13-18. RESULTS: Between 2007-2009, 14 patients enrolled, 12 were evaluable. Nine patients were on study at 12 weeks. Objective responses (by RECIST and/or CA125) occurred in 4 patients. There were no grade 4, and only four grade 3 toxic events: diarrhea, edema and 2 cases of neutropenia. Early study closure was due to sufficient safety information with preliminary encouraging efficacy results. CONCLUSION: This weekly paclitaxel regimen with intermittent IM is tolerable with anti-tumor activity, making it suitable as part of future studies
— id: 113816, year: 2010, vol: 30, page: 3243, stat: Journal Article,

A phase I trial of dose-dense (biweekly) carboplatin combined with paclitaxel and pegfilgrastim: a feasibility study in patients with untreated Stage III and IV ovarian, tubal or primary peritoneal cancer: a Gynecologic Oncology Group study
Tiersten, Amy D; Sill, Michael W; Knight, Danielle; Muggia, Franco; Garcia, Agustin A; Swensen, Ron; Warshal, David P; Mannel, Robert S; Fracasso, Paula M
2010 Sep;118(3):303-307, Gynecologic oncology
PURPOSE: Dose-dense regimens have been shown to improve outcome when given as adjuvant therapy to patients with breast cancer compared with their three weekly counterparts. We investigated the feasibility of a dose-dense regimen with carboplatin/paclitaxel followed by pegfilgrastim in patients with advanced ovarian cancer. We also investigated the toxicities including the percentage of patients with grade 2 or greater peripheral neurotoxicity and the clinical response of this regimen. PATIENTS AND METHODS: Women with untreated Stage III or IV epithelial ovarian, (fallopian) tubal, or primary peritoneal cancer were treated with carboplatin area under the curve (AUC) 5 and paclitaxel 175 mg/m(2) day one, and pegfilgrastim 6 mg day two every 2 weeks for six cycles. RESULTS: Between 9/06 and 9/08, 43 patients enrolled. Thirty-one patients completed six or more cycles of therapy. The dose limiting toxicities resulting in treatment discontinuation included: grade 3 and 4 neuropathy, grade 4 thrombocytopenia, grade 4 thrombocytopenia/grade 3 febrile neutropenia, and grade 4 supraventricular tachycardia. Twelve patients (30%) had >or=grade 2 neuropathy from this regimen. The overall response rate in patients with measurable disease was 58% (11 out of 19). CONCLUSION: Dose-dense carboplatin/paclitaxel appears to be effective. However, based on dose limiting toxicities occurring when administering 6 cycles of treatment, it is not feasible. Given the neuropathy and thrombocytopenia, we do not recommend 6 cycles of this regimen without modification
— id: 111685, year: 2010, vol: 118, page: 303, stat: Journal Article,

Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009
Tiersten, Amy D; Liu, P Y; Smith, Harriet O; Wilczynski, Sharon P; Robinson, William R 3rd; Markman, Maurie; Alberts, David S
2009 Mar;112(3):444-449, Gynecologic oncology
OBJECTIVE: Intraperitoneal (IP) chemotherapy prolongs survival in optimally reduced ovarian cancer patients. For patients in whom optimal debulking cannot be achieved, one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy. We sought to evaluate overall survival (OS), progression-free survival (PFS), percent of patients optimally debulked and toxicity in patients treated with this strategy. METHODS: Women with adenocarcinoma by biopsy or cytology with stage III/IV (pleural effusions only) epithelial ovarian, fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery (if >/=50% decrease in CA125). If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 (day 1) and IP paclitaxel 60 mg/m2 (day 8) q 28 daysx6 cycles. RESULTS: Sixty-two patients were registered. Four were ineligible. Fifty-six were evaluated for neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients had grade 4 toxicity, including neutropenia (3), anemia, leukopenia, anorexia, fatigue, muscle weakness, respiratory infection, and cardiac ischemia. Thirty-six patients had debulking surgery. Two had grade 4 hemorrhage. Twenty-six patients received post-cytoreduction chemotherapy. Four had grade 4 neutropenia. At a median follow-up of 21 months, median PFS is 21 months and median OS is 32 months for all 58 patients. PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively. CONCLUSIONS: These results compare favorably with other studies of sub-optimally debulked patients
— id: 95015, year: 2009, vol: 112, page: 444, stat: Journal Article,

Chemotherapy resistance as a predictor of progression-free survival in ovarian cancer patients treated with neoadjuvant chemotherapy and surgical cytoreduction followed by intraperitoneal chemotherapy: a Southwest Oncology Group Study
Tiersten, Amy D; Moon, James; Smith, Harriet O; Wilczynski, Sharon P; Robinson, William R 3rd; Markman, Maurie; Alberts, David S
2009 ;77(6):395-399, Oncology (New York)
PURPOSE: In vitro testing of the activity of chemotherapeutic agents has been suggested as 1 method to optimally select drugs for patients with ovarian cancer. There are limited prospectively obtained data examining the clinical utility of this approach. We sought to obtain a preliminary assessment of this strategy in a trial that examined the administration of neoadjuvant chemotherapy followed by surgical cytoreduction and intraperitoneal chemotherapy in women with advanced ovarian cancer. METHODS: Women with stage III/IV epithelial ovarian carcinoma that presented with large-volume disease were treated with neoadjuvant intravenous paclitaxel and carboplatin for three 21-day cycles followed by cytoreductive surgery. If optimally debulked, patients received intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel for six 28-day cycles. Tumor cloning assay results (Oncotech) were correlated with progression-free survival. RESULTS: Sixty-two patients (58 eligible) were registered from March 2001 to February 2006. Thirty-six eligible patients had interval debulking and 26 received postcytoreduction chemotherapy. Twenty-two patients had tumor cloning assay results available. The clinical features of this population were similar to those of the larger group of women who entered this study. There was no difference in progression-free survival between patients whose cancers were defined as 'resistant' or 'nonresistant' to either platinum or paclitaxel. CONCLUSIONS: While the small patient numbers in this trial do not permit definitive conclusions, these data fail to provide support for the argument that prospectively obtained in vitro data regarding platinum or paclitaxel resistance will be highly predictive of clinical outcome in advanced ovarian cancer
— id: 111626, year: 2009, vol: 77, page: 395, stat: Journal Article,

Randomized trial of low-dose interleukin-2 vs cyclosporine A and interferon-gamma after high-dose chemotherapy with peripheral blood progenitor support in women with high-risk primary breast cancer
Vahdat, L T; Cohen, D J; Zipin, D; Lo, K S; Donovan, D; Savage, D; Tiersten, A; Nichols, G; Troxel, A; Hesdorffer, C S
2007 Aug;40(3):267-272, Bone marrow transplantation
High-risk primary breast cancer patients treated with high-dose chemotherapy (HDC) and stem cell support (SCS) have shown prolonged disease-free survival (DFS) in many studies; however, only one trial has demonstrated an overall survival benefit (OS). We hypothesize that the period following myeloablative therapy is ideal for immunologic manipulation and studied the effects of two different methods of immunotherapy following HDC with SCS aimed at the window of immune reconstitution. Seventy-two women with high-risk stage II or III breast cancer were randomized following HDC to receive either interleukin 2 (IL-2) at 1 million units/m(2) SQ daily for 28 days or combined cyclosporine A (CsA) at 1.25 mg/kg intravenously daily from day 0 to +28 and interferon gamma (IFN-gamma) 0.025 mg/m(2) SQ every 2 days from day +7 to +28. At a median follow-up of 67 months, no significant difference was observed in DFS or OS between the two treatment groups. The IL-2 arm had a 59% DFS (95% CI (0.45, 0.78)) and a 72% OS (95% CI (0.58, 0.88)) at 5 years. The CsA/INF-gamma arm had a similar outcome with a 55% DFS (95% CI (0.40, 0.76)) and a 78% OS (95% CI (0.65, 0.94)) at 5 years. Treatment was well tolerated, without increased toxicity
— id: 74322, year: 2007, vol: 40, page: 267, stat: Journal Article,

Report of first-stage accrual for NCI 5886, a phase II study of erlotinib, carboplatin and paclitaxel as first-line treatment of ovarian cancer
Blank, SV; Curtin, JP; Goldman, NA; Runowicz, CD; Speyer, JL; Tiersten, AD; Dancey, J; Wadler, S; Muggia, FM
2006 JUN 20 ;24(18):274S-274S, Journal of clinical oncology
— id: 69299, year: 2006, vol: 24, page: 274S, stat: Journal Article,

Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer
Tiersten, A; Selleck, M; Smith, D H; Wertheim, I; Kaufman, E; Hershman, D; Vahdat, L T; Savage, D G; MacArthur, R B; Hesdorffer, C
2006 Jan-Feb;16(1):57-64, International journal of gynecological cancer
The objectives of this study were to investigate the tolerability of a novel high-dose chemotherapy (HDC) regimen with peripheral blood progenitor cell (PBPC) support in patients with pretreated advanced ovarian cancer and to determine the maximum-tolerated dose (MTD) of topotecan in this setting. Advanced ovarian cancer patients previously treated with platinum-based first-line therapy were enrolled. After PBPC mobilization and harvesting, patients received three consecutive cycles of HDC with PBPC support. Cycle 1 was carboplatin area under the concentration curve 20 and paclitaxel 250 mg/m(2). Cycle 2 was topotecan starting at 5 mg/m(2), dose escalated in 2 mg/m(2) increments, and etoposide 600 mg/m(2). Cycle 3 was thiotepa 500 mg/m(2). After each cycle, PBPCs were infused. Granulocyte colony stimulating factor (5 microg/kg/day) was administered until neutrophil recovery occurred. Seventeen patients were enrolled; all were safety evaluable. The most common nonhematologic toxicity was grade 3 mucositis (44%). Engraftment of PBPCs was successful in all patients after each cycle, and no treatment-related deaths occurred. Of 14 patients with measurable disease, 5 (36%) had complete responses, 2 (14%) had partial responses, and 4 (29%) had stable disease. The median progression-free and overall survivals were 7 and 18 months, respectively. The MTD of topotecan was not reached. The tolerability and activity of this regimen in patients with advanced ovarian cancer warrant further investigation
— id: 89514, year: 2006, vol: 16, page: 57, stat: Journal Article,

Long natural history of recurrent granulosa cell tumor of the ovary 23 years after initial diagnosis: a case report and review of the literature
Crew, Katherine D; Cohen, Michael H; Smith, Daniel H; Tiersten, Amy D; Feirt, Nikki M; Hershman, Dawn L
2005 Jan;96(1):235-240, Gynecologic oncology
BACKGROUND: Granulosa cell tumors (GCTs) of the ovary are rare, hormonally active neoplasms characterized by endocrine manifestations, an indolent course, and late relapse. CASE: We report a case of a prolonged history of ovarian GCT managed primarily with repeat surgical resections. CONCLUSION: This case illustrates the benefits of cytoreductive surgery for the management of recurrent disease, the use of serum tumor markers to help guide therapy, and the importance of extended follow-up
— id: 89515, year: 2005, vol: 96, page: 235, stat: Journal Article,

Recreational exercise and quality of life among women undergoing adjuvant chemotherapy for breast cancer
Jacobson, CA; Talbot, SM; Vahdat, LT; Troxel, AB; Shriberg, L; Bralman, LB; Tiersten, AD
2004 JUL 15 ;22(14):777S-777S, Journal of clinical oncology
— id: 48691, year: 2004, vol: 22, page: 777S, stat: Journal Article,

Phase II study of topotecan and paclitaxel for recurrent, persistent, or metastatic cervical carcinoma
Tiersten, Amy D; Selleck, Meredith J; Hershman, Dawn L; Smith, D; Resnik, Edward E; Troxel, Andrea B; Brafman, Lois B; Shriberg, Laureen
2004 Feb;92(2):635-638, Gynecologic oncology
OBJECTIVE: This trial investigated the safety and efficacy of paclitaxel and topotecan combination chemotherapy for patients with advanced cervical cancer (ACC). METHODS: Patients with recurrent, persistent, or metastatic ACC and an ECOG performance status < or =2 were treated with 175 mg/m(2) paclitaxel on Day 1 and 1 mg/m(2) topotecan on Days 1-5 of a 21-day cycle with G-CSF support and the standard pretreatment regimen for paclitaxel. Patients were treated until disease progression or unacceptable toxicity. RESULTS: Fifteen patients were enrolled, and 86 cycles of therapy (median, 5; range, 1-14) were administered. Grade 3/4 toxicities included anemia (47%), leukopenia (27%), neurotoxicity (13%), thrombocytopenia (13%), and diarrhea (13%). Among 13 evaluable patients, 7 (54%) responded (1 complete and 6 partial; 95% confidence interval = 29.2%, 76.8%). Three (23%) patients experienced stable disease. Progression-free and overall survival were 3.77 and 8.62 months, respectively. CONCLUSION: The combination of paclitaxel/topotecan was generally well tolerated and active in the relapsed, recurrent, or metastatic ACC setting, with response rates comparable with those of other current ACC systemic therapies
— id: 45326, year: 2004, vol: 92, page: 635, stat: Journal Article,

Relationship between mammographic breast density and tamoxifen in women with breast cancer
Tiersten, Amy; Ng, Yin Y; Pile-Spellman, Eliza; Nelsen, Caron; Noguera-Irizarry, Wanda; Brafman, Rebecca; Russo, Donna; Troxel, Andrea; Johnson, Alan
2004 Jul-Aug;10(4):313-317, Breast journal
Previous studies have reported that tamoxifen use is associated with a decrease in mammographic breast density. This is a potentially valuable finding since mammographic sensitivity is limited by breast density. Anything that reduces breast density would theoretically enhance the sensitivity of mammography for the detection of breast cancer in women at an earlier stage when it is more curable. We performed a retrospective study investigating the potential effect of tamoxifen on breast density. The data for this retrospective study were collected from the records of 52 charts from a single medical oncologist. Patients with breast cancer were selected regardless of stage or age at the time of diagnosis or treatment, as long as their charts had records of bilateral mammograms. For each breast on each woman, both mediolateral oblique and craniocaudal views were reviewed independently by two radiologists on two separate occasions to obtain inter- and intraobserver variability. Two methods of classifying breast density were used: the Breast Imaging Reporting and Data System (BI-RADS), and measurements of percent density. Only age and menopausal status were found to be associated with breast density. There was no correlation between breast density and tamoxifen use (past or present). Our study shows no association between tamoxifen use and breast density. We confirm previous observations that breast density is inversely correlated with age and postmenopausal status
— id: 45325, year: 2004, vol: 10, page: 313, stat: Journal Article,

Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer
Tiersten, Amy; Wo, Jennifer; Jacobson, Caron; Weitzman, Aaron; Horwich, Tamara; Hesdorffer, Charles; Savage, David; Troxel, Andrea
2004 Aug;13(4):341-346, Breast
INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development
— id: 45324, year: 2004, vol: 13, page: 341, stat: Journal Article,

Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer
Hershman, Dawn; Weinberg, Mitchell; Rosner, Zachary; Alexis, Karenza; Tiersten, Amy; Grann, Victor R; Troxel, Andrea; Neugut, Alfred I
2003 Oct 15;95(20):1545-1548, Journal of the National Cancer Institute
Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage-matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 x 10(9)/L for African American women versus 7.4 x 10(9)/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P =.02) and after treatment (5.3 x 10(9)/L for African American women versus 6.4 x 10(9)/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P =.03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P =.03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival
— id: 45327, year: 2003, vol: 95, page: 1545, stat: Journal Article,

A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma
Tiersten, Amy D; Nelsen, Caron; Talbot, Susan; Vahdat, Linda; Fine, Robert; Troxel, Andrea; Brafman, Lois; Shriberg, Laureen; Antman, Karen; Petrylak, Daniel P
2003 Feb 1;97(3):537-544, Cancer
BACKGROUND: The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-express P-glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC). METHODS: Thirty-six patients with MBC were treated with estramustine 900 mg/m(2) per day divided into 3 doses given on Days 1-3 and docetaxel 70 mg/m(2) given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC. RESULTS: Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14-48%). The median progression free survival was 4 months (range, 1-41 months), and the median overall survival was 17 months (range, 2-45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy-five percent of patients experienced either an improvement or no change in quality of life. CONCLUSIONS: The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life
— id: 45328, year: 2003, vol: 97, page: 537, stat: Journal Article,

Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer
Vahdat, L T; Balmaceda, C; Papadopoulos, K; Frederick, D; Donovan, D; Sharpe, E; Kaufman, E; Savage, D; Tiersten, A; Nichols, G; Haythe, J; Troxel, A; Antman, K; Hesdorffer, C S
2002 Aug;30(3):149-155, Bone marrow transplantation
A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease
— id: 45329, year: 2002, vol: 30, page: 149, stat: Journal Article,

Complementary and alternative medicine: the role of the cancer center
Antman K; Benson MC; Chabot J; Cobrinik D; Grann VR; Jacobson JS; Joe AK; Katz AE; Kelly K; Neugut AI; Russo D; Tiersten A; Weinstein IB
2001 Sep 15;19(18 Suppl):55S-60S, Journal of clinical oncology
— id: 45330, year: 2001, vol: 19, page: 55S, stat: Journal Article,

Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326)
Rothenberg ML; Liu PY; Wilczynski S; Hannigan EV; Weiner SA; Weiss GR; Hunter VJ; Chapman JA; Tiersten A; Kohler PC; Alberts DS
2001 Aug;82(2):317-322, Gynecologic oncology
OBJECTIVE: The aim of this study was to evaluate the 2-year survival rate in a group of women in complete clinical remission (cCR) from Stage III ovarian cancer following front-line therapy who were then treated with a 6-month course of altretamine. METHODS: Patients were documented to be in cCR by physical examination, computed tomography or magnetic resonance imaging scan, and serum CA-125. Treatment consisted of altretamine (Hexalen) 260 mg/m(2)/day po divided into four doses taken after meals and at bedtime for 14 of 28 days for six cycles. Based on previous experience in the Southwest Oncology Group, the treatment would be considered promising if the 2-year survival rate was > or = 65% as measured from study registration. RESULTS: From 9/1/93 and 7/1/97, 112 patients were registered and 97 were fully evaluable. The majority of patients had optimally debulked (< or = 1 cm: 63%), high-grade (Grade 3: 82%) tumors. The 2-year survival rate in this study was 75% (95% CI: 66-84%). For those patients with optimal disease, the 2-year survival rate was 82% (95% CI: 72-92%) and for those with suboptimal disease it was 64% (95% CI: 48-79%). Four patients (4%) experienced Grade 4 and 21 patients (22%) experienced Grade 3 toxicities consisting primarily of nausea/vomiting, neutropenia, fatigue, anxiety, and paresthesias. CONCLUSIONS: The 2-year survival rate in this study warrants further evaluation of consolidation therapy for women in clinical complete remission following front-line chemotherapy for Stage III ovarian cancer. Caution is advised in the interpretation of these data, however, because of the nonrandomized nature of the trial and the unknown contribution of front-line use of paclitaxel to the durability of clinical complete response
— id: 45331, year: 2001, vol: 82, page: 317, stat: Journal Article,

Reduction of paclitaxel-induced peripheral neuropathy with glutamine
Vahdat L; Papadopoulos K; Lange D; Leuin S; Kaufman E; Donovan D; Frederick D; Bagiella E; Tiersten A; Nichols G; Garrett T; Savage D; Antman K; Hesdorffer CS; Balmaceda C
2001 May;7(5):1192-1197, Clinical cancer research
PURPOSE: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose paclitaxel. EXPERIMENTAL DESIGN: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m(2) given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. RESULTS: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P < 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. CONCLUSIONS: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity
— id: 45332, year: 2001, vol: 7, page: 1192, stat: Journal Article,

High-dose chemotherapy for breast cancer: evolving data
Antman K; Tiersten A
1999 Sep;13(9):1215-1219, Oncology
— id: 45333, year: 1999, vol: 13, page: 1215, stat: Journal Article,

Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer
Vahdat LT; Papadopoulos K; Balmaceda C; McGovern T; Dunleavy J; Kaufman E; Fung B; Garrett T; Savage D; Tiersten A; Ayello J; Bagiella E; Heitjan D; Antman K; Hesdorffer C
1998 Jul;4(7):1689-1695, Clinical cancer research
A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity
— id: 45335, year: 1998, vol: 4, page: 1689, stat: Journal Article,

Influence of inflammatory bowel disease on the ability of patients to tolerate systemic fluorouracil-based chemotherapy
Tiersten A; Saltz LB
1996 Jul;14(7):2043-2046, Journal of clinical oncology
PURPOSE: To evaluate the safety of administering fluorouracil (5FU)-based chemotherapy to cancer patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: We retrospectively reviewed all patients entered into the Memorial Sloan-Kettering Cancer Center clinical data base from 1985 through 1995 who had a diagnosis of IBD, had a gastrointestinal malignancy, and were treated with systemic 5FU-based chemotherapy. A total of 19 patient charts were identified and reviewed. RESULTS: Fifty-three percent of patients reviewed experienced severe (grade III/IV) diarrhea on treatment. Sixty percent of patients with a history of active IBD and 40% of patients with a history of inactive IBD experienced severe diarrhea on treatment. The incidence of severe diarrhea did not appear to be substantially influenced by age, schedule of 5FU administration, concurrent radiation, or type of IBD. CONCLUSION: While there does appear to be an increased risk of diarrhea exacerbation in IBD patients treated with 5FU, a substantial number of patients tolerate chemotherapy without increased difficulty. The degree of IBD activity or other clinical parameters can not be used to predict accurately the likelihood of toxicity
— id: 45336, year: 1996, vol: 14, page: 2043, stat: Journal Article,

Acute hypertensive crisis following octreotide administration in a patient with maligantn pheochromocytoma
Saltz L; Tiersten A; Hassan B; Groger J
1995 ;2:1129-1130, Oncology reports
— id: 45339, year: 1995, vol: 2, page: 1129, stat: Journal Article,

Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer
Seidman AD; Tiersten A; Hudis C; Gollub M; Barrett S; Yao TJ; Lepore J; Gilewski T; Currie V; Crown J
1995 Oct;13(10):2575-2581, Journal of clinical oncology
PURPOSE: To evaluate the efficacy and safety of paclitaxel administered by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Forty-nine patients with metastatic breast cancer received paclitaxel via 3-hour intravenous infusion after standard premedication. Prophylactic granulocyte colony-stimulating factor (G-CSF) was not used, and chemotherapy was cycled every 3 weeks. For 25 patients who received paclitaxel as initial therapy (group I), the starting dose was 250 mg/m2. Twenty-four patients who had received two or more prior regimens, including an anthracycline (group II), started at 175 mg/m2. Paclitaxel pharmacokinetics were evaluated in 23 patients in group I. RESULTS: Grade 3 and 4 toxicities included (groups I/II) neutropenia (36%/33%), thrombocytopenia (0%/8%), anemia (0%/13%), neuropathy (8%/0%), arthralgia/myalgia (16%/4%), and mucositis (4%/4%). No significant hypersensitivity-type reactions or cardiac arrhythmias were seen. Six patients who received paclitaxel at > or = 250 mg/m2 experienced transient photopsia, without apparent chronic neuro-ophthalmologic sequelae. The mean peak plasma paclitaxel concentration was 5.87 mumol/L (range, 1.99 to 7.89) for these patients, and 6.08 mumol/L (range, 0.81 to 13.81) for 17 of 19 patients who did not experience visual symptoms. In 25 assessable patients in group I at a median follow-up time of 12 months, one complete response (CR) and seven partial responses (PRs) have been observed, for a total response rate of 32% (95% confidence interval [CI], 15% to 53%). In group II, five PRs were noted in 24 assessable patients (20.8%; 95% CI, 7% to 42%). Median response durations were 7 months for group I and 4 months for group II. CONCLUSION: Paclitaxel via 3-hour infusion, without prophylactic G-CSF, is active and safe as initial and subsequent therapy for metastatic breast cancer. The transient visual symptoms noted at higher doses seem unrelated to peak plasma paclitaxel concentration. Further studies that compare 3- and 24 hour (or other) infusion schedules are necessary to determine the optimal administration of paclitaxel in metastatic breast cancer
— id: 45337, year: 1995, vol: 13, page: 2575, stat: Journal Article,

Rapidly cycled courses of high-dose alkylating agents supported by filgrastim and peripheral blood progenitor cells in patients with metastatic breast cancer
Vahdat L; Raptis G; Fennelly D; Hamilton N; Reich L; Tiersten A; Harrison M; Hudis C; Moore M; Yao TJ
1995 Nov;1(11):1267-1273, Clinical cancer research
Our purpose was to determine the feasibility of a regimen of multiple, rapidly cycled courses of high-dose alkylating agents, including paired courses of escalating doses of thiotepa, supported by peripheral blood progenitor cells and filgrastim, in patients with responding stage IV breast cancer. The regimen consisted of two courses of cyclophosphamide (3.0 g/m2/course) followed by two courses of thiotepa (500-700 mg/m2/course). All courses were supported by filgrastim. Leukaphereses were performed after each cyclophosphamide course to harvest peripheral blood progenitors (PBPs) for use as rescue following thiotepa administration. The planned interval for all courses was 14 days. Forty-two patients were enrolled. Thirty-eight received all four courses, and four did not receive the second thiotepa cycle due to poor PBP mobilization. The maximum dose of thiotepa that was administered was 700 mg/m2 x 2. At this dose, one patient developed encephalopathy, which resolved over several weeks. The median number of days to an absolute neutrophil count of 0.5 x 10(9)/liter after PBP reinfusion for cycles 1 and 2 of thiotepa were 9 (range, 7-16) and 9 (range, 8-13) days, respectively. The corresponding values for platelet recovery to >20 x 10(9)/liter were 11 (range, 8-39) and 12 (range, 10-28) days, respectively. There were no treatment-related deaths. Hospitalization was required following 28 of 84 cyclophosphamide courses and 76 of 80 thiotepa courses. Four patients developed grade III-IV mucositis. The median interval between courses of treatment was 15 (range, 13-29) days. Of 19 patients who entered the protocol with measurable disease in partial response from prior therapy, 8 (42%) achieved complete response following the high-dose therapy. Nine (21%) of 42 remain progression free at a median follow-up of 28 (range, 20-32) months. Therefore, we concluded that the administration of multiple, rapidly cycled courses of high-dose alkylating agents is feasible
— id: 45334, year: 1995, vol: 1, page: 1267, stat: Journal Article,

Prospective follow-up for malignant melanoma in patients with atypical-mole (dysplastic-nevus) syndrome
Tiersten AD; Grin CM; Kopf AW; Gottlieb GJ; Bart RS; Rigel DS; Friedman RJ; Levenstein MJ
1991 Jan;17(1):44-48, Journal of dermatologic surgery & oncology
A total of 357 white patients who had melanocytic nevi that fulfilled the clinical criteria for the 'classic' atypical-mole (dysplastic-nevus) syndrome (100 or more melanocytic nevi; one or more melanocytic nevi 8 mm or larger in diameter; and, one or more melanocytic nevi with atypical features) were followed for the development of cutaneous malignant melanomas. Seventeen patients (4.8%) developed malignant melanomas during an average follow-up period of 49 months. One patient developed two malignant melanomas. Eight of the malignant melanomas detected were in situ and ten were invasive melanomas (less than 0.86 mm in Breslow thickness), implying an excellent prognosis. The number of malignant melanomas detected in these patients exceeded significantly the number expected to occur in age- and sex-matched white controls. All groups were shown to have an increased risk for the development of malignant melanomas. Total-body photographs were helpful in detecting changes in size, shape, and color that led to the diagnosis of malignant melanoma. These data support the concept that patients with this readily regionalized clinical presentation of classic atypical-mole syndrome are at an increased risk for malignant melanomas and, therefore, should be examined regularly
— id: 8192, year: 1991, vol: 17, page: 44, stat: Journal Article,