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Devika Gajria,
Joseph Gonzalez,
Kimberly Feigin,
Sujata Patil,
Carol Chen,
Maria Theodoulou,
Pamela Drullinsky, Gabriella D'Andrea,
Diana Lake,
Larry Norton,
Clifford A Hudis,
Tiffany A Traina
[show abstract]
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ABSTRACT: Our group applied mathematical modeling to capecitabine dosing and predicted 7 days of treatment followed by 7 days of rest (7-7) would improve efficacy and minimize toxicity. The conventional schedule of capecitabine limits full dosing in combination with other agents due to toxicity. Lapatinib inhibits the tyrosine kinase of HER2 and has activity when added to conventionally scheduled capecitabine for the treatment of patients with trastuzumab-refractory, HER2-positive, metastatic breast cancer (MBC). We performed this study to evaluate the activity and tolerability of capecitabine 7-7 with lapatinib in patients with trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC that progressed following exposure to trastuzumab. Treatment consisted of capecitabine 2,000 mg orally twice daily, 7-7 and lapatinib 1,250 mg orally daily. The primary endpoint was response rate. Secondary endpoints included toxicity, progression-free survival, and stable disease ≥ 6 months. Twenty-three patients were treated on study. More than 60% had prior chemotherapy for MBC and all had prior trastuzumab. After a median of 23 weeks (range 2-96+), five patients had partial responses (23; 95 CI, 7-44%) and six (27; 95 CI, 10-48%) had stable disease ≥ 6 months. Median progression-free survival was 9.4 months. The most common treatment-related toxicities ≥ grade (gr) 2 were hand-foot syndrome (gr 2 43%; gr 3 4% gr 4 0%), diarrhea (gr 2 26%; gr 3/4 0%), elevated liver chemistries (gr 2 17%; gr 3/4 0%), and anemia (gr 2 13%; gr 3 4%; gr 4 4%). No grade ≥ 3 nausea, vomiting, or diarrhea events occurred. This study demonstrated feasibility and after meeting biostatistical requirements for continued accrual was terminated in anticipation of slow enrollment. Capecitabine 7-7 with lapatinib was well tolerated with minimal gastrointestinal toxicity. Antitumor activity was observed in patients with trastuzumab-refractory MBC.
Breast Cancer Research and Treatment 09/2011; 131(1):111-6. · 4.43 Impact Factor
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Shanu Modi,
Alison Stopeck,
Hannah Linden,
David Solit,
Sarat Chandarlapaty,
Neal Rosen, Gabriella D'Andrea,
Maura Dickler,
Mary E Moynahan,
Steven Sugarman,
Weining Ma,
Sujata Patil,
Larry Norton,
Alison L Hannah,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer.
We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28).
This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted.
Clinical Cancer Research 05/2011; 17(15):5132-9. · 7.74 Impact Factor
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Heather L McArthur,
Hope Rugo,
Benjamin Nulsen,
Laura Hawks,
Jill Grothusen,
Michelle Melisko,
Mark Moasser,
Matthew Paulson,
Tiffany Traina,
Sujata Patil, [......],
Nancy Sklarin,
Mark Robson,
Mary Ellen Moynahan,
Steven Sugarman,
Jane E Sealey,
John H Laragh,
Carmen Merali,
Larry Norton,
Clifford A Hudis,
Maura N Dickler
[show abstract]
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ABSTRACT: Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer.
Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC → nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted.
The median age was 48 years (range, 27-75 years), and baseline LVEF was 68% (53%-82%). After 39 months' median follow-up (5-45 months): median LVEF was 68% (53%-80%) at 2 months (n = 78), 64% (51%-77%) at 6 months (n = 66), 63% (48%-77%) at 9 months (n = 61), and 66% (42%-76%) at 18 months (n = 54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted congestive heart failure (CHF) or HTN, respectively.
Bevacizumab with ddAC → nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials.
Clinical Cancer Research 02/2011; 17(10):3398-407. · 7.74 Impact Factor
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Pamela Drullinsky,
Steven M Sugarman,
Monica N Fornier, Gabriella D'Andrea,
Teresa Gilewski,
Diana Lake,
Tiffany Traina,
Carolyn Wasserheit-Lieblich,
Nancy Sklarin,
Deena Atieh-Graham,
Nancy Mills,
Tiffany Troso-Sandoval,
Andrew D Seidman,
Jeffrey Yuan,
Hamangi Patel,
Sujata Patil,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule.
Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%.
The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals.
Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.
Clinical Breast Cancer 12/2010; 10(6):440-4. · 2.38 Impact Factor
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Alison K Conlin,
Andrew D Seidman,
Ariadne Bach,
Diana Lake,
Maura Dickler, Gabriella D'Andrea,
Tiffany Traina,
Michael Danso,
Adam M Brufsky,
Mansoor Saleh,
Alicia Clawson,
Clifford A Hudis
[show abstract]
[hide abstract]
ABSTRACT: This multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC).
We treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m2 and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles.
The overall response rate (ORR) was 62.5% (95% CI, 45.7%-79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%).
Weekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.
Clinical Breast Cancer 08/2010; 10(4):281-7. · 2.38 Impact Factor
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Steven Sugarman,
Carolyn Wasserheit,
Elizabeth Hodgman,
Maryellen Coglianese,
Anne D'Alassandro,
Monica Fornier,
Tiffany Troso-Sandoval, Gabriella D'Andrea,
Pamela Drullinsky,
Diana Lake,
Roshini George,
Nancy Mills,
Maryellen Moynahan,
Joyce Smith,
Katherine Panageas,
Larry Norton,
Clifford Hudis
Breast Cancer Research and Treatment 08/2009; · 4.43 Impact Factor
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[show abstract]
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ABSTRACT: Cancer patients commonly use dietary supplements to "boost immune function". A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown.
In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days -7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability.
No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose-response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses.
Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.
Journal of Cancer Research and Clinical Oncology 03/2009; 135(9):1215-21. · 2.56 Impact Factor
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Chau Dang, Gabriella D'Andrea,
Diana Lake,
Steve Sugarman,
Monica Fornier,
Mary Ellen Moynahan,
Theresa Gilewski,
Arti Hurria,
Nancy Mills,
Tiffany Troso-Sandoval,
Roshini George,
Mark Robson,
Maura Dickler,
Karen Smith,
Katherine S Panageas,
Larry Norton,
Clifford A Hudis
[show abstract]
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ABSTRACT: We conducted a pilot study of dose-dense epirubicin/cyclophosphamide (EC) x 6 --> paclitaxel (P) x 6 with pegfilgrastim. A previous dose-dense trial of FEC (5-fluorouracil [5-FU]/EC) x 6 with filgrastim --> by weekly paclitaxel alternating with docetaxel x 18 was not feasible because of pneumonitis (with dose-dense FEC) and pericardial/pleural effusion (taxane phase). Dose-dense EC (without the 5-FU) is not associated with pneumonitis, and dose-dense paclitaxel (alone) is feasible. Primary objective was feasibility.
Patients with resectable breast cancer were enrolled, regardless of surgery status, tumor size, or nodal status. Treatment regimen consisted of every-2-week EC (100/600 mg/m2) x 6 --> by 2-weekly P (175 mg/m2) x 6 with pegfilgrastim 6 mg on day 2.
Between November 2004 and May 2005, 38 patients were enrolled. The median age was 47 years (range, 30-72 years); 33 of 38 (87%) were treated in the adjuvant setting and 27 of 33 (81%) had involved nodes (range, 1-46); 5 of 38 (13%) were treated pre-operatively; 33 of 38 (87%) completed all chemotherapy as planned; the remaining patients (13%) had treatment modifications for toxicity. Febrile neutropenia occurred in 6 of 38 patients (16 %) and only during EC. There were 12 hospitalizations in 9 of 38 patients (24%) enrolled.
Dose-dense every-2-week EC x 6 --> P x 6 with pegfilgrastim is feasible based on our prospective definition.
Clinical Breast Cancer 10/2008; 8(5):418-24. · 2.38 Impact Factor
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Steven Sugarman,
Carolyn Wasserheit,
Elizabeth Hodgman,
Maryellen Coglianese,
Anne D'Alassandro,
Monica Fornier,
Monica Fournier,
Tiffany Troso-Sandoval, Gabriella D'Andrea,
Pamela Drullinsky,
Diana Lake,
Roshini George,
Nancy Mills,
Maryellen Moynahan,
Joyce Smith,
Katherine Panageas,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Granulocyte-colony stimulating factor (G-CSF) was used in CALGB 9741 to support dose-dense sequential chemotherapy with doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) (Citron et al. J Clin Oncol 21:1431-1439, 2003). However, myelosuppression is not known to be dose or schedule limiting for paclitaxel. We therefore conducted this trial to determine the need for routine G-CSF, using the pegylated product (pG-CSF), support during the paclitaxel component of dose-dense sequential chemotherapy in women with early stage breast carcinoma (BC).
Eligible patients received dose-dense chemotherapy consisting of four cycles of AC followed by four cycles of P at two week intervals. pG-CSF (Neulasta) was administered after each of four cycles of AC but was held after P. Planned enrollment was 59 pts.
Of the first 15 patients, nine completed therapy without delays due to neutropenia but 6 (40%) did not, leading to implementation of the pre-specified early termination rule. Overall, 85% of P doses were successfully delivered on time. The mean treatment delay for the entire group due to neutropenia was 0.75 days. There was no significant correlation between neutropenia and prior WBC, ANC, or concurrent treatment with trastuzumab. Pts with neutropenia tended to be younger (Mean age 43.5) and have a lower BSA (1.65 m(2)). There were no febrile episodes due to omission of pG-CSF.
When paclitaxel is administered in a dose-dense fashion without growth factor support brief treatment delays are common. Further study is needed to identify the minimal pG-CSF administration that will avoid treatment delays.
Breast Cancer Research and Treatment 09/2008; 115(3):609-12. · 4.43 Impact Factor
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Chau Dang,
Monica Fornier,
Steven Sugarman,
Tiffany Troso-Sandoval,
Diana Lake, Gabriella D'Andrea,
Andrew Seidman,
Nancy Sklarin,
Maura Dickler,
Violante Currie,
Theresa Gilewski,
Mary Ellen Moynahan,
Pamela Drullinsky,
Mark Robson,
Carolyn Wasserheit-Leiblich,
Nancy Mills,
Richard Steingart,
Katherine Panageas,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival.
Patients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of >or= 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m(2)) x 4 followed by P (175 mg/m(2)) x 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T x1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18.
From January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced congestive heart failure (CHF). There were no cardiac deaths.
Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.
Journal of Clinical Oncology 04/2008; 26(8):1216-22. · 18.37 Impact Factor
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Monica N Fornier,
Andrew D Seidman,
Diana Lake, Gabriella D'Andrea,
Jacqueline Bromberg,
Mark Robson,
Catherine Van Poznak,
Katherine S Panageas,
Marietta Atienza,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics.
Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m(2) epirubicin and 600 mg/m(2) cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m(2) paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 microg s.c. daily) from day 2 to 24 h before the next treatment.
Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38 degrees C with absolute neutrophil count <1,000/microL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting.
Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The approximately 30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.
Clinical Cancer Research 02/2007; 13(1):223-7. · 7.74 Impact Factor
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Arti Hurria,
Mark T Fleming,
Sharyn D Baker,
Wm Kevin Kelly,
Katie Cutchall,
Katherine Panageas,
James Caravelli,
Henry Yeung,
Mark G Kris,
Jorge Gomez,
Vincent A Miller, Gabriella D'Andrea,
Howard I Scher,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the pharmacokinetics of weekly docetaxel in a cohort of older patients with metastatic cancer and to explore the relationship of pharmacokinetic variables, Erythromycin Breath Test results, age, geriatric assessment variables, and toxicity to therapy.
Twenty patients ages > or = 65 years with metastatic breast, prostate, or lung cancer entered an Institutional Review Board-approved protocol to evaluate the pharmacokinetics of weekly docetaxel administered at 35 mg/m2 i.v. for 3 weeks followed by a 1-week break. The Erythromycin Breath Test and geriatric assessment were done before the first dose. Blood samples were collected for pharmacokinetic analysis with the first dose of docetaxel.
Of the 20 patients who entered the study, 19 were evaluable. There were no age-related differences in the pharmacokinetics of weekly docetaxel. Fifty-eight percent (11 of 19) experienced grade > or = 3 toxicity: 16% (3 of 19) grade > or = 3 hematologic toxicity, and 53% (10 of 19) grade > or = 3 nonhematologic toxicity. There was an association between the Erythromycin Breath Test results and docetaxel pharmacokinetic variables; however, there was no association between Erythromycin Breath Test results or docetaxel pharmacokinetics with frequency of grade > or = 3 toxicity.
Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade > or = 3 toxicity at the 35 mg/m2 starting dose. We advocate a starting dose of 26 mg/m2 on this weekly schedule and dose escalating if no toxicity.
Clinical Cancer Research 10/2006; 12(20 Pt 1):6100-5. · 7.74 Impact Factor
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[show abstract]
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ABSTRACT: The epidermal growth factor receptor (EGFR) is part of the ErbB family of receptor tyrosine kinases and is known to be variably expressed in breast cancers. Cetuximab is a humanized monoclonal antibody directed against the EGFR that works by blocking the downstream signaling function of this protein and thereby interfering with cancer cell proliferation. Preclinical studies have indicated a synergistic effect for the combination of anti-EGFR therapy plus paclitaxel in breast cancer models.
Hence, we conducted a dose-escalation phase I trial using cetuximab/paclitaxel in patients with metastatic breast cancer to evaluate the feasibility of this combination. Patients with EGFR-positive metastatic breast cancer treated with <or= 1 previous therapy, excluding taxanes, were eligible. Treatment consisted of weekly cetuximab therapy and every-3-week paclitaxel, with dose escalation of cetuximab until the maximum tolerated dose was reached.
Twelve patients were enrolled to 3 treatment cohorts. Two of 6 patients on the second cohort (cetuximab 100 mg/m2) developed dose-limiting toxicities, presenting as grade 3 rash. The third cohort was amended to allow the same cetuximab dose but to modify the paclitaxel to a weekly schedule. Despite this, 1 of 3 patients in this group also developed grade 3 skin toxicity as a dose-limiting toxicity; thus, the trial was stopped. Ten of the 12 patients were evaluable for response, and of these, 2 patients experienced stable disease, and 8 patients experienced disease progression.
Because of prohibitive dermatologic toxicity and disappointing preliminary efficacy, the combination of paclitaxel/cetuximab was not considered promising in this population, although further study of this regimen might be warranted.
Clinical Breast Cancer 08/2006; 7(3):270-7. · 2.38 Impact Factor
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Arti Hurria,
Anju Hurria,
Enid Zuckerman,
Katherine S Panageas,
Monica Fornier, Gabriella D'Andrea,
Chau Dang,
Mark Moasser,
Mark Robson,
Andrew Seidman,
Violante Currie,
Catherine VanPoznak,
Maria Theodoulou,
Mark S Lachs,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: To examine the toxicity experienced by a cohort of older women receiving adjuvant chemotherapy for breast cancer and the longitudinal effect on their functional status and quality of life (QOL).
A geriatric assessment measuring functional status, comorbidity, mood, nutritional status, and QOL was performed before chemotherapy, at the end of chemotherapy, and 6 months later.
This prospective longitudinal study was conducted at Memorial Sloan-Kettering Cancer Center, New York, New York.
Fifty patients aged 65 and older with Stage I to III breast cancer receiving any adjuvant chemotherapy; 49 were evaluable.
The chemotherapy regimen and the toxicity to chemotherapy were recorded. A geriatric assessment was performed before the start of chemotherapy, on completion of chemotherapy, and 6 months after completion of chemotherapy. QOL testing was performed at the same times.
Patients (mean age 68, range 65-84) received an anthracycline-based chemotherapy regimen (n=15) or cyclophosphamide 600 mg/m2 intravenously (i.v.), methotrexate 40 mg/m2 i.v., 5-fluorouracil 600 mg/m2 i.v. every 3 weeks for eight cycles (n=34). Grade 3 or 4 toxicity occurred in 53% (n=26), hematological toxicity in 27% (n=13), and nonhematological toxicity in 31% (n=15). Despite toxicity, there was no significant longitudinal change in functional status or QOL.
Despite toxicity from adjuvant chemotherapy, this cohort of relatively young older patients maintained their functional status and QOL from before chemotherapy to 6 months postchemotherapy. Subtle changes in higher-order functioning would require assessment using different geriatric assessment tools.
Journal of the American Geriatrics Society 08/2006; 54(7):1119-24. · 3.74 Impact Factor
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Arti Hurria,
Shari Goldfarb,
Carol Rosen,
Jimmie Holland,
Enid Zuckerman,
Mark S Lachs,
Matthew Witmer,
Wilfred G van Gorp,
Monica Fornier, Gabriella D'Andrea,
Mark Moasser,
Chau Dang,
Catherine Van Poznak,
Mark Robson,
Violante E Currie,
Maria Theodoulou,
Larry Norton,
Clifford Hudis
[show abstract]
[hide abstract]
ABSTRACT: This longitudinal prospective study describes the older breast cancer patient's perception of the cognitive impact of adjuvant chemotherapy.
A total of 50 patients > or =age 65 with stage I to III breast cancer enrolled in this IRB-approved prospective study. Of the 50, 3 refused postchemotherapy testing and 2 had a cerebrovascular accident (CVA) during therapy, leaving 45 evaluable patients. The Squire Memory Self-Rating Questionnaire, given before and 6 months after chemotherapy, measured patients' perceptions of the ability to learn new information, of working memory, and of remote learning capabilities.
Mean age was 70 years (range 65-84). Breast cancer stages were: I (33%), II (64%), III (2%). A 51% (23/45) of study participants perceived a decline in memory from before to 6 months after completion of chemotherapy. Patients who perceived a poorer memory than average before chemotherapy were more likely to report further memory deterioration after chemotherapy (19/30, 63%) than patients who perceived that their memory was average or better than average prior to chemotherapy (4/15, 27%). The memory domain most likely to be perceived as affected was the ability to learn new information (22/45, 49%) compared to remote memory (9/45, 20%) or working memory (13/45, 29%) capabilities.
Approximately half of these older women perceived a decline in cognitive function from before to 6 months after chemotherapy. This perceived decline in cognitive function was most pronounced in patients with preexisting memory complaints. Further prospective study is needed to confirm these observations, correlate perceived memory changes with objective findings, and identify subgroups at special risk.
Breast Cancer Research and Treatment 08/2006; 98(3):343-8. · 4.43 Impact Factor
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Arti Hurria,
Carol Rosen,
Clifford Hudis,
Enid Zuckerman,
Katherine S Panageas,
Mark S Lachs,
Matthew Witmer,
Wilfred G van Gorp,
Monica Fornier, Gabriella D'Andrea,
Mark Moasser,
Chau Dang,
Catherine Van Poznak,
Anju Hurria,
Jimmie Holland
[show abstract]
[hide abstract]
ABSTRACT: To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer.
Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy.
Cancer center.
Thirty-one patients aged 65 and older with Stage I to III breast cancer. Of the 31 patients enrolled, three refused post-testing, and 28 were evaluable.
The following domains of cognitive function were examined: attention; verbal memory; visual memory; and verbal, spatial, psychomotor, and executive functions.
Participants had a mean age of 71 (range 65-84): 39% Stage I, 50% Stage II, and 11% Stage III. The number of scores 2 standard deviations (SDs) below the norm were calculated for each patient before and 6 months after chemotherapy; 14 (50%) had no change, 11 (39%) worsened, and three (11%) improved (P=.05). Seven patients (25%) experienced a decline in cognitive function, defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains. Exploratory analyses revealed no significant difference between functional status, comorbidity, and depression scale scores and change in overall quality-of-life scores before and after chemotherapy.
In this cohort of older women receiving adjuvant chemotherapy, a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy. Further prospective study is needed to confirm these observations and to identify the subgroup at special risk.
Journal of the American Geriatrics Society 07/2006; 54(6):925-31. · 3.74 Impact Factor
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Arti Hurria,
Carol Rosen,
Clifford Hudis,
Enid Zuckerman,
Katherine S. Panageas,
Mark S. Lachs,
Matthew Witmer,
Wilfred G. Van Gorp,
Monica Fornier,
D&apos,
Gabriella Andrea,
Mark Moasser,
Chau Dang,
Catherine Van Poznak,
Anju Hurria,
Jimmie Holland, Gabriella D'Andrea
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ABSTRACT: OBJECTIVES: To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer.DESIGN: Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy.SETTING: Cancer center.PARTICIPANTS: Thirty-one patients aged 65 and older with Stage I to III breast cancer. Of the 31 patients enrolled, three refused posttesting, and 28 were evaluable.MEASUREMENTS: The following domains of cognitive function were examined: attention; verbal memory; visual memory; and verbal, spatial, psychomotor, and executive functions.RESULTS: Participants had a mean age of 71 (range 65–84): 39% Stage I, 50% Stage II, and 11% Stage III. The number of scores 2 standard deviations (SDs) below the norm were calculated for each patient before and 6 months after chemotherapy; 14 (50%) had no change, 11 (39%) worsened, and three (11%) improved (P=.05). Seven patients (25%) experienced a decline in cognitive function, defined as a 1-SD decline from pre- to posttesting in two or more neuropsychological domains. Exploratory analyses revealed no significant difference between functional status, comorbidity, and depression scale scores and change in overall quality-of-life scores before and after chemotherapy.CONCLUSION: In this cohort of older women receiving adjuvant chemotherapy, a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy. Further prospective study is needed to confirm these observations and to identify the subgroup at special risk.
Journal of the American Geriatrics Society 05/2006; 54(6):925 - 931. · 3.74 Impact Factor
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Shanu Modi,
Andrew D Seidman,
Maura Dickler,
Mark Moasser, Gabriella D'Andrea,
Mary Ellen Moynahan,
Jennifer Menell,
Katherine S Panageas,
Lee K Tan,
Larry Norton,
Clifford A Hudis
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ABSTRACT: Imatinib mesylate is a potent inhibitor of Abl, KIT, and PDGFR tyrosine kinases. Breast cancer has variable expression of KIT and PDGFR therefore we conducted a phase II trial to evaluate the safety and efficacy of imatinib in patients with metastatic breast cancer (MBC).
Eligible patients had measurable and progressive MBC, with no limits on prior chemo- or hormonal therapy. Imatinib was initially administered at a dose of 400 mg orally twice a day with provisions for dose reductions based on toxicities. The primary endpoint was clinical benefit based on RECIST criteria. Tumor specimens were tested for expression of KIT and PDGFR tyrosine kinases.
Sixteen patients were enrolled and treated. Median age was 55 years (range: 35-73); median number of prior chemotherapy regimens for MBC was 4 (range 1-8). The main non-hematologic toxicities were (Grades 1/2; Grade 3): fatigue (56%; 6%), edema (38%; 19%), nausea (31%; 19%), vomiting (38%; 0%), anorexia (38%; 0%), diarrhea (19%; 6%), and rash (25%; 6%). Grade 3/4 hematologic and biochemical abnormalities were minimal. There was no evidence of clinical benefit. The median duration of therapy on trial was 28 days (range 2-71). Of the 13 testable cases: 1 was KIT positive and 4 were PDGFR positive.
Imatinib therapy at doses of 800 mg/day was associated with significant toxicity in patients with heavily pre-treated MBC. Our results do not indicate activity for imatinib monotherapy in these unselected patients.
Breast Cancer Research and Treatment 04/2005; 90(2):157-63. · 4.43 Impact Factor
