tbuckley/cabot-search huggingface dataset:
A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: NCCTG study N04CA.
Authors: C. L. Loprinzi, E. P. Balcueva, H. Liu, L. A. Kottschade, P. J. Stella, M. D. Carlson, D. F. Moore, R. Zon, R. Levitt, J. A. Sloan
Journal: Journal of Clinical Oncology (2010)

9024 Background: Vaginal dryness is a common problem, for which effective and safe non-estrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness (Arch Intern Med 159:174-81, 1999), the current trial was conducted. Methods: A double-blind, placebo (PLCB)-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, to a PLCB. Patients (pts) must have had persistent vaginal dryness and/or itching of sufficient severity to desire therapeutic intervention. Vaginal dryness was recorded by pt-completed questionnaires at baseline and weekly for 6 weeks. The primary endpoint was the area under the curve (AUC) summary statistic comprised of the longitudinal responses obtained at baseline and through the 6 weeks of treatment to a 0-10 numerical analogue scale, asking pts to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t-test using a two-sided alternative and 5% Type I error to compare the collective pilocarpine treatment arms versus the collective PLCB arms. The two-sample t-test for the primary analysis, with 128 pts in the pilocarpine arms and 64 pts in the PLCB arm, had 80% power to detect a difference of 50% times the standard deviation. Results: 201 pts (195 evaluable) were enrolled in this trial; 64, 65, and 66 pts in the PLCB, lower dose pilocarpine and higher dose pilocarpine treatment arms. The primary analysis, comparing vaginal dryness symptoms, did not reveal any benefit for the collective pilocarpine arms or either of the individual pilocarpine treatment arms, all compared to the PLCB arm, with each group improving from about 42/100 to about 72/100 (all p>0.424). At the end of the study, 27 (54%), 27 (50%), and 31 (53%) of the pts stated that they had improvements in vaginal dryness in the PLCB, lower dose pilocarpine, and higher dose pilocarpine treatment arms (p = 0.132). Toxicity evaluation revealed more rigors (p = 0.002), urinary frequency (p = 0.006), nausea (p = 0.030), and sweating (p = 0.062) in the pilocarpine arms, compared to the PLCB arm. Conclusions: Pilocarpine did not alleviate vaginal dryness, yet did cause some toxicity. No significant financial relationships to disclose.
Nasal allergen provocation test in nasal polyposis with and without allergy
Authors: Lien Calus, Lien Devuyst, Natalie De Ruyck, Thibaut Van Zele, Claus Bachert, Philippe Gevaert
Journal: Allergy (2013)

Methods Four groups of patients (n=48) underwent nasal allergen provocation test for grass pollen. We included 12 patients with allergic rhinitis based on grass allergy, 12 patients with CRSwNP without grass allergy, 12 patients with CRSwNP with grass allergy, and 12 control patients. The diagnosis of grass allergy was based on skin prick test and RAST. The test was positive based on change in nasal airflow measured by active anterior rhinomanometry and symptoms. In annex, VAS scores were performed before and after NAPT.
Weekly cisplatin-epirubicin-paclitaxel with G-CSF support in ER-negative large operable breast cancer. The NCI of Naples’ nine-year experience
Authors: G. Frasci, G. D'Aiuto, P. Comella, R. Thomas, G. Iodice, G. Botti, M. Di Bonito, M. D'Aiuto, M. Rubulotta, G. Comella
Journal: Journal of Clinical Oncology (2008)

577 Background: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with ER-negative large operable breast cancer after the administration of 8 cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of initial population were updated, with inclusion of additional experience with the same therapy. Methods: Patients with ER-negative large operable breast cancer (T2-T3 N0–1; T>3 cm) received 8 preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel 120 mg/m2, with G-CSF (5 microgr/kg days 3–5) support. Results: Overall 71 consecutive patients (T2/T3 = 28/43; N0/N+=23/48) were treated. Nineteen patients were HER-2 positive. At pathologic assessment, 48 patients (67.6%) showed absence of invasive residual disease in breast and 49 (69%) had negative axilla. In 43 women (60.6%; 95%C.I.=48–72) both breast and axilla were found disease free. At a 37-month median follow-up (range; 2–101), 14 relapses (3 local-regional and 11 distant), and 6 deaths have occurred, 5-year projected RFS and OS being 79% and 92%, respectively. Grade 3–4 neutropenia and anemia occurred in 19 (27%) and 5 (7%) patients, respectively. Emesis, diarrhea, and mucositis were quite frequent; however, each of them was severe in less than 10% of patients. Peripheral neuropathy was quite frequent but never severe. Conclusions: Eight weekly PET cycles are a very effective preoperative approach in women with ER-negative large operable breast cancer. This triplet regimen deserves to be evaluated in further phase III trials. No significant financial relationships to disclose.
Stereotactic radio-surgery in the treatment of brain metastases from radio-resistant tumors
Authors: A. Narayana, S. Patil, S. Diamond, Y. Yamada, P. H. Gutin
Journal: Journal of Clinical Oncology (2005)

1552 Background: Melanoma and renal cell carcinoma are generally considered resistant to conventional fractionated radiation. However, there is some evidence that suggests that they may respond better to higher dose per fraction. We retrospectively studied the clinical outcome of melanoma and renal cell carcinoma (RCC) patients who were treated with single fraction stereotactic radiosurgery (SRS) for metastatic lesions in the brain. Methods: Forty-nine melanoma patients with 92 lesions and 20 RCC patients with 27 lesions received SRS as the primary method of treatment for their brain metastases. Treatment spanned from January of 2001 through December of 2003, with a minimum follow up of 1 year. SRS was delivered using a 6MV linear accelerator using mini-micro multileaf collimation. The median dose prescribed was 2100cGy (range 1400–2400 cGy) based on tumor size. Patients were monitored with serial MRI’s that were done every three months to measure local control, development of new metastases and radiation necrosis. Results: The local control of the treated lesions was worse in melanoma when compared to RCC (6 months 72% Vs 83%, 1-year 50% vs. 71%; p=0.02). Development of new brain metastases was the dominant method of intracranial failure in both groups (Median time 3.9 vs. 4.0 months; p=NS). Survival was dismal in both the groups when measured from the date of SRS (Median 6.0 Vs 6.9 months p=NS). Radiation dose was the only factor that correlated with improved local control (p>0.002) for both sites. Karnofsky status of > 90 and Age < 70 turned out to be better prognostic indicators for increased survival at the time of SRS. Addition of whole brain radiation therapy had no impact on either local control or survival in either tumor. The incidence of radiation necrosis was higher in melanoma when compared to RCC (9.8% Vs 2.4%). Conclusions: Response to single fraction SRS is different between RCC and melanoma. The improved local control with SRS did not translate into improved survival in RCC due to failure at other sites in the brain as well as progression of systemic disease. Failure in the brain as well as radiation necrosis still remains a concern with melanoma. No significant financial relationships to disclose.
Bendamustine/mitoxantrone/rituximab (BMR): A very effective and well tolerated immuno-chemotherapy for relapsed and refractory indolent lymphomas. Results of a multicentre phase-II study of the German Low Grade Lymphoma Study Group (GLSG)
Authors: R. Weide, J. Heymanns, J. Thomalla, H. Köppler, G. Hess, A. Aldaoud, S. Schmitz, M. Unterhalt, M. H. Dreyling, W. Hiddemann
Journal: Journal of Clinical Oncology (2005)

6616 In a previous phase I study we could demonstrate that the combination of the two chemotherapeutic agents bendamustine and mitoxantrone in combination with the lymphocyte-specific antibody rituximab (BMR) is a highly effective regimen in the treatment of relapsed or refractory indolent lymphomas and CLL (Leukemia and Lymphoma 2002, 43(2):327–331). Based on these data a multicenter phase II study further evaluated the efficacy and toxicity of BMR. BMR consisted of Bendamustine 90mg/m2 (days 1+2), Mitoxantrone 10mg/m2 (day 1) and Rituximab 375mg/m2 (day 8). Treatment was repeated on day 29 for a total of 4 cycles. Between 04/03 and 07/04, 46 patients (pts) with symptomatic stage III/IV indolent lymphomas were treated with BMR (19 follicular, 14 mantle cell, 3 marginal zone, 4 B-CLL, 2 immunocytoma, 1 patient with hairy cell leukemia, 2 patients with secondary large cell lymphoma and 1 patient with a secondary aggressive NHL not otherwise specified). All pts were treated on an outpatient basis. Median age was 66.5 years (40 - 83) and their performance score ranged from 0–2. Median number of previous regimens was 1 (1–8). 19 pts (41%) had rituximab pretreatment. Grade 3/4 hematotoxicity occurred in 36 pts (78%), no treatment related death was reported. Currently, 41 pts are evaluable: the overall response rate (ORR) was 93% with 40% complete remissions and 53% partial remissions. ORR in rituximab pretreated patients was 88% (56% CR, 31% PR). The median follow up for the treated patients is 5 months (range: 2–15 months). Seven cases of progression after start of initial therapy have been observed until now. We conclude that BMR is a very effective and well tolerated immuno-chemotherapy for relapsed or refractory indolent lymphomas. A high response rate was seen in patients who were pretreated with rituximab. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ribosepharm Germany, Roche Germany ribosepharm Germany, Roche, Roche Germany
Neoadjuvant dose-dense sequential biweekly epirubicin and cyclophosphamide followed by docetaxel and trastuzumab for HER2+ operable breast cancer
Authors: L. Blakely, B. Somer, M. Keaton, R. Hermann, F. Schnell, P. Cobb, A. Johns, M. Walker, L. Schwartzberg
Journal: Journal of Clinical Oncology (2009)

595 Background: Neoadjuvant (Neo) chemotherapy (CT) with trastuzumab (H) improves pathologic complete response (pCR) rate for HER2+ breast cancer. Dose-dense regimens improve outcome in the adjuvant setting but have not been fully evaluated as preoperative therapy. We designed this regimen to utilize full doses of active agents including docetaxel (T) and H in a novel biweekly schedule to explore efficacy and safety. Methods: Patients (pts) with biopsy proven, clinical stage IIA-IIIC, noninflammatory breast cancer were eligible. HER2+ by FISH was determined locally. CT consisted of epirubicin (E) 100 mg/m2 and cyclophosphamide (C) 600 mg/m2 Q 14 days x 4 followed by T 75 mg/m2 and H 6 mg/kg loading dose, then 4 mg/kg Q 14 days x 4, all with pegfilgrastim support. Surgery was scheduled 20–24 weeks from start after a fifth cycle of H 4mg/kg. EF was measured prior to CT, after EC, after TH and at 6, 12 and 24 months after surgery. Additional adjuvant H to complete 1 year of therapy by conventional schedule was recommended after surgery. The primary endpoint was pCR for invasive cancer in breast and lymph nodes. Results: 30 pts were enrolled at 5 centers: median age was 50.1 (range, 31–72); ethnicity African-American 14, Caucasian 14, other 2; clinical stage IIA, 14, IIB, 4, IIIA, 7, IIIB/C, 5; ER+ 18, PR+ 14; grade 3, 21 and grade 2, 8. Twenty eight pts were evaluable for pathologic response- 2 withdrew before completing treatment, 1 for toxicity. Dose delivery on schedule was &gt;95% for all drugs. Clinical response prior to surgery was cCR 20; cPR 5; and stable 2 pts. Pathologic response: pCR 16 (57%) including 4 with residual DCIS only; 9 pPR, and 2 stable. Mean EF was 63.1 (range, 51–81) before treatment, 62.4 (49–75) after EC and 58.3 (35–74) after TH. Two pts had EF &lt;50% during Neo, one with clinical CHF and 1 additional pt developed CHF during adjuvant single agent H. Both pts had symptomatic improvement with cessation of H. Adverse events were generally mild with 14 grade 3 AEs including 3 episodes of dyspnea and no grade 3 skin toxicity or any grade 4 toxicity noted. Conclusions: Sequential Neo dose-dense Q 14 day EC followed by Q 14 day TH yields a high pCR rate in HER2+ breast cancer with acceptable toxicity profile and no new safety signals noted. No significant financial relationships to disclose.
Comparison of ER, PR, HER2 in primary and paired relapsed/metastatic lesions of metastatic breast cancer patients
Authors: E. Sari, G. Guler, M. Hayran, K. Altundag, I. Gullu, Y. Ozisik
Journal: Journal of Clinical Oncology (2009)

1063 Background: The assessment of ER, PR and HER2 is made routinely in every breast cancer patient to have information about prognosis and to select patients (pts) who are candidates for hormonal and anti-HER2 therapy. Recent studies have shown some degrees of discordance in ER, PR, and HER-2 expression between primary and recurrent/metastatic lesions (RML). In this study we compared the ER, PR, and HER2 status of the primary and paired RML in metastatic breast cancer pts. Methods: Analysis was made on 79 metastatic breast cancer pts whose ER, PR, and/or HER2 status were known both on the tissue samples of primary and RML. ER, PR, and HER2 status were determined by immunohistochemistry and/or fluorescence-in-situ hybridization. Results: Among the RML sites, 24% were locoregional, 76% were distant metastatic sites. Among 72 pts with known ER expression on both primary and RML, 36% showed discordance on ER expression. Most of the change occurred from negative to positive ER status (15 of 48 ER positive primaries had ER negative paired metastasis and 11 of 24 ER negative primaries had ER positive paired metastasis). Among 68 pts with known PR expression on both primary and RML, 51.5% showed discordance on PR expression. Change in PR status from positive to negative and negative to positive was similar (23 of 45 PR positive primaries had PR negative paired metastasis and 12 of 23 PR negative primaries had PR positive paired metastasis). Among 58 pts with known HER2 expression on both primary and RML, 15.5% showed discordance on HER2 expression. Six pts with HER-2 negative primaries, showed HER2 overexpression in their paired RML. Four pts who had HER2 overexpressing primary did not show HER2 expression in the paired RML. Conclusions: A proportion of pts show discordances in hormonal receptor and HER2 expression between the primary tumor and the paired RML. As these discordant results make changes in treatment decision, a biopsy of the metastatic lesion could be recommended in metastatic breast cancer pts when feasible. No significant financial relationships to disclose.
Secondary surgical cytoreduction and hyperthermic intraperitoneal chemoperfusion (SSC-HIPEC) for recurrent gynecologic malignancies
Authors: L. Randall-Whitis, C. W. Helm, C. R. Toler, R. S. Martin, D. S. Metzinger, R. P. Edwards
Journal: Journal of Clinical Oncology (2004)

5096 Background: Survival of women with recurrent gynecologic cancers remains poor with traditional treatments. Intraperitoneal hyperthermic chemotherapy following surgical surgical cytoreduction of intra-abdominal tumor (SSC-HIPEC) has not been widely used to treat gynecologic cancers despite promising results in recurrent gastrointestinal cancers. Our aim was to evaluate its safety and efficacy in this group of patients. Methods: Patients undergoing SSC-HIPEC at our institution 2002–2003 were identified and retrospective chart review was performed to determine pre-operative indications, peri-operative course, morbidity, and outcome. Results: Ten patients underwent SSC-HIPEC. Median age was 60 yr. (37–73), and primary disease sites were ovarian =6, endometrial=3, and primary peritoneal=1. All patients had previously been heavily treated with primary surgery and multiple chemotherapies. Closed-system intraperitoneal perfusion of cisplatin (100 mg/m2) heated to a minimum of 40oC (104o) for 90 minutes was performed following cytoreductive surgery. Mean operative time was 9.7 hours (6–14 hrs) and mean blood loss 1000cc (350–2400cc). Post-operatively, mean return to bowel function was 5.8 days (3–8 d) and mean length of hospital stay was 11.2 days (7–16 d). Peri-operative morbidities included UTI=1, pneumonia=1, fistula=1, pleural effusion=1, and grade 1–2 renal toxicity=2. There were no peri-operative deaths. 8 patients (80%) have no evidence of disease at 4–11 months post-operatively. Conclusions: SSC-HIPEC is well tolerated by heavily pre-treated patients with recurrent gynecologic cancer, and has potential to significantly prolong survival. This treatment warrants further investigation as a second-line therapy in a Phase II design. No significant financial relationships to disclose.
Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: An international phase II study
Authors: E. Díaz Rubio, J. Tabernero, E. van Cutsem, A. Cervantes, T. André, Y. Humblet, P. Soulié, S. Corretgé, O. Kisker, A. de Gramont
Journal: Journal of Clinical Oncology (2005)

3535 Background: Cetuximab (Erbitux), an IgG1 monoclonal antibody that specifically targets EGFR the receptor, is effective in combination with irinotecan or irinotecan/5-FU/FA in patients with EGFR-expressing mCRC in the first and second-/subsequent-line settings. The study was designed to evaluate the safety and efficacy of cetuximab in combination with FOLFOX-4 as first-line treatment. Methods: Pts with non-resectable EGFR-expressing mCRC, with no prior chemotherapy, were treated with cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus FOLFOX-4 (every 2 weeks: oxaliplatin 85 mg/m2, day 1; FA 200 mg/m2 IV 2h and 5-FU 400 mg/m2 IV bolus followed by 600 mg/m2 IV for 22h, days 1 and 2) until progressive disease (PD) or unacceptable toxicity. Preliminary Results: Of the 62 pts, median ECOG performance status 0 (0–2), screened, 52 pts (84%) had EGFR-expressing metastatic disease, 43 pts, median age 65 yrs (range 43–78) were finally enrolled. All of the patients are assessable for safety and efficacy. Main adverse events grade 3/4 (pts ≥10%, multiple cycle) observed per pt: acne-like rash 30.2%, diarrhea 25.6%, neurotoxicity 25.6%, neutropenia 20.9%, stomatitis/mucositis 16.3%. The efficacy data on 42 pts yielded an overall confirmed response rate of 72%, comprising 4 (9%) complete responses (CR) and 27 (63%) partial responses (PR). There were also 10 (23%) pts with stable disease to yield a disease control rate of 95%. 8 pts are still on treatment. PFS is 10.2 months. To date, 10 pts have undergone surgery of their metastases: 8 for liver, 1 for lung, 1 for suprarenal gland metastases (9 R0 resections). Conclusions: The combination of cetuximab and FOLFOX-4 has an acceptable safety profile and demonstrates advantages in response rate in the first-line treatment of patients with EGFR-expressing mCRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, Merck KGaA Amgen, Baxter, Roche, sanofi-aventis Merck KGaA Bristol-Myers Squibb, Lilly Oncology, Merck, Roche, sanofi-aventis Lilly Oncology, Roche, sanofi-aventis
The association between clinical, sociodemographic, and logistic-administrative factors and adherence to completing health-related quality-of-life questionnaires.
Authors: J. Vercauteren, J. Maringwa, C. Coens, C. Quinten, C. Gotay, J. Ringash, M. King, D. Osoba, H. Flechtner, A. Bottomley
Journal: Journal of Clinical Oncology (2010)

9075 Background: Health-related quality of life (HRQOL) is an integral part of many clinical cancer trials. However, one of the challenges remains understanding key factors responsible for low adherence to completing patient self-reported HRQOL questionnaires. Methods: Retrospective pooling of 29 European Organisation for Research and Treatment of Cancer (EORTC) randomized controlled phase III trials (RCTs), among 11 cancer sites, yielded baseline data from 10,060 patients, including clinical variables: pretreatment (none vs. only surgery vs. systemic treatment),WHO performance status, distant metastasis, median survival time per trial (reflecting the average prognosis per trial) and cancer site; socio-demographic variables: age and gender and logistic-administrative variables: start date of the trial (1990-2004), rank of patient randomized in the trial (per center) and accrual volume per center. Adherence, defined as completing the QLQ-C30 forms at baseline, was studied via multiple logistic regression. Results: Cancer patients were more adherent if their performance status was higher (OR = 1.12; 95%CI: 1.02-1.24: p = 0.02), if they had a history of systemic treatment or cancer surgery (respectively OR = 2.44; 95%CI: 1.95-3.05: p<0.01 and OR = 2.41; 95%CI: 2.04-2.84: p<0.01) and if they had distant metastasis (OR = 2.25; 95%CI: 1.90-2.66: p<0.01). Patients who had a shorter median survival time showed lower adherence (OR = 0.67; 95%CI: 0.63-0.72: p<0.01). Age and gender did not have a significant impact (p<0.05) on baseline HRQOL adherence. However, adherence improved over the years (OR = 1.40; 95%CI: 1.36-1.44: p<0.01) and by increasing accrual per center (OR = 1.15; 95%CI: 1.08-1.22: p<0.01). Finally, adherence decreased when randomized later into a trial (OR = 0.82; 95%CI: 0.76-0.89: p<0.01). Conclusions: Adherence to completing HRQOL questionnaires in EORTC RCTs has improved significantly over the years; however continuous monitoring of good quality of life assessment at the center level should be stimulated. Our analysis identified key factors for adherence that can be useful for future planning of international RCTs. No significant financial relationships to disclose.