tbuckley/cabot-search huggingface dataset:
Phase I study of bortezomib plus cetuximab in patients with tumors expressing epidermal growth factor receptor (EGFR)
Authors: A. Dudek, P. Gada, K. Mulamalla, N. Shehadeh
Journal: Journal of Clinical Oncology (2007)

18143 Background: Bortezomib is a proteasome inhibitor that augments EGFR inhibitor activity (Cancer Research 2007; 67:(2),1–8). Cetuximab is a chimeric mouse-human antibody against EGFR that has been found to induce tumor responses in patients with colon cancer and head and neck cancer. The purpose of this study was to establish a maximum tolerated dose (MTD) for the combination of bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumors. Methods: A 21-day treatment cycle was given with a maximum of six cycles per patient. Bortezomib was administered intravenously on days 1 and 8 via dose escalation, beginning with a minimum dose of 1.3 mg/m 2 and increasing in one-tenth increments to 2.0 mg/m 2 for a total of eight dose levels. Cetuximab was delivered with an initial dose of 400mg/m 2 on day 1 cycle 1, with subsequent doses of 250mg/ m 2 on days 1, 8 and 15. Results: Twenty patients (13 male and 7 female) with an ECOG PS &lt;2 were enrolled in this study from November 2005 to December 2006. The median age was 59.5 (range: 41- 68), and the median number of prior chemotherapy regimens was 5 (range 1–7). Primary tumor sites included lung (9), head and neck (4), kidney (3), pancreas (2), bladder (1), and ovary (1). A total of 54 cycles of chemotherapy were administered; the median number of cycles per patient was 2.5 (range 1–6). Thirteen patients discontinued therapy because of disease progression. Two patients completed all six cycles of therapy. One dose-limiting toxicity (DLT) was seen at dose level 4 (bortezomib 1.6 mg/m 2 ), which included grade 3 nausea, vomiting and dysphagia based on evaluation using CTCAE (version 3.0). Level 4 was expanded to enroll 3 additional patients, and no further grade 3 or 4 toxicities were observed. Grade 3 / 4 non- hematological toxicities were observed in 14 patients after their first cycle of therapy. Nine patients had delay in treatment. Conclusions: MTD for bortezomib plus cetuximab was not achieved at dose levels 1–6. This combination therapy has shown limited clinical activity in our extensively pretreated group of patients with solid tumors. Complete results for all dose levels, including dose levels 7–8, will be reported at the 2007 meeting of the American Society of Clinical Oncology. [Table: see text]
Evaluation of the influence of physical problems, emotional problems, and extent of disease on the distress level (DL) in breast cancer (BC) women
Authors: I. Cedrych, A. Heyda, B. Lukaszczk-Widel, B. Lange, A. Syska-Bielak, K. Skladowski
Journal: Journal of Clinical Oncology (2009)

e20628 Background: Despite recent treatment advances, BC diagnosis is still synonymous to death, and suffering and provides emotional impairment in most of patients. Thus the distress assessment and management is the essential component of comprehensive BC patient care.The aim of the study was to recognize DL in the group of BC patients (pts) at the different stages of the disease and treatment period and to evaluate the most important distress causes and sources. Methods: In 60 BC women (median age 58 years, range: 37–86) diagnosed within last two years, the measurement of distress level was performed using the Distress Thermometer scale with the problem list attached, according to NCCN practice quidelines recommendation for distress assessment. The median time from the diagnosis to the distress data collecting moment was 3.9 months. Most pts were postmenopausal (70%), have positive family cancer history (60%) and suffered from other diseases (75%); 45% of them presented stage III of BC (stage I - 26%, II - 23%, IV - 5%). Chemotherapy received 55% of pts, surgical treatment 65% and radiotherapy 46%. At the moment of DL evaluation 61% of pts were remained free from BC symptoms and 72% from strong stressful event during last year. Results: The median DL in the whole group was 5 (range 0–10) and in 76% of pts the level was 4 or higher. Problem-list evaluation revealed that 96% of pts had physical, 90% emotional, 38% practical and 20% family problems. Both univariate and multivariate analysis revealed the independent and positive correlation with DL for: physical problems (p=0.000009), peripheral blood granulocytes level (p=0.000024), strong-stressful event passed during the last year (p=0.005) sadness (p=0.01) The surgical cancer treatment was correlated with DL negatively (p=0.008). Conclusions: DL evaluation has shown that the DL was associated mostly with practical, emotional and physical problems and the history of personal stressful event in the near past. BC surgery is a strong source of anti-distress. These data indicate a need of DL assessment with not neglecting the individual medical and psychosocial history of each patient to provide best psychological support, expecially in women who are not qualified to, or are before surgery. No significant financial relationships to disclose.
Activity of single agent temsirolimus (CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes
Authors: S. M. Smith, B. Pro, A. Cisneros, S. Smith, P. Stiff, E. Lester, S. Modi, J. E. Dancey, E. E. Vokes, K. van Besien
Journal: Journal of Clinical Oncology (2008)

8514
Dose-intensive CHOP chemotherapy followed by radiation for localized NK/T-cell lymphoma
Authors: S.-H. Ji, S.-H. Lee, J. H. Kim, K. Kim, W. S. Kim, J. O. Park, C. W. Jung, W. K. Kang, M. H. Lee, K. Park
Journal: Journal of Clinical Oncology (2004)

6716 Background: NK/T-cell lymphoma is a specific type of T-cell lymphoma which is prevalent in Eastern Asia and known to have poor prognosis. With the hope of better treatment outcome, we developed new induction regimen using dose-escalated doxorubicin and cyclophosphamide, and higher dose-intensity. Methods: Newly diagnosed, modified Ann-Arbor stage I and II, NK-T cell lymphoma patients were enrolled. We planned to treat them with 2 cycles of dose-intensive CHOP (DI-CHOP), followed by radiation (total 40 Gy with 20 fractions) and 4 cycles of conventional CHOP. DI-CHOP consisted of cyclophosphamide (1250 mg/m2, day 1), doxorubicin (75 mg/m2, day 1), vincristine (1.4 mg/m2, day 1) and prednisolone (100 mg/day for 5 days) with growth factor support (G-CSF 150 ug/day for 10 days). The second cycle of DI-CHOP was started as soon as possible when ANC more than 1500/uL and platelet count more than 75,000/uL no less than 14 days since day 1 of the first cycle. Results: From March 2000 to May 2003, consecutive 12 patients were accrued. Ten patients (83%) completed 2 cycles of DI-CHOP and radiation. Seven patients (58%) completed all planned treatment. The interval between the first and second cycle of DI-CHOP was 14 to 23 days (median, 14 days). Eight patients (67%) achieved complete remissions and three patients (25%) partial remissions. With median follow-up duration of 14.9 months, four patients (33%) experienced relapses and no patient died in relation to disease progression. Eight patients (67%) experienced grade 4 neutropenia and four patients (33%) febrile neutropenia during DI-CHOP. One patient experienced septic shock leading to treatment-related mortality. Conclusions: Dose-intensive induction CHOP preceding radiation was a feasible approach against localized NK/T-cell lymphoma, but short follow-up and small number of accrual limit us to conclude this approach is more effective than conventional CHOP induction. No significant financial relationships to disclose.
Mitochondrial DNA variation and genetic structure in Old-World populations of Drosophila subobscura.
Authors: J M Afonso, A Volz, M Hernandez, H Ruttkay, M Gonzalez, J M Larruga, V M Cabrera, D Sperlich
Journal: Molecular Biology and Evolution (1990)

To discover the relation between mitochondrial DNA (mtDNA) polymorphism and the geographic population structure of Drosophila subobscura previously established for other genetic traits, a wide Paleartic survey was carried out. A total of 24 nucleomorphs was observed among 261 isofemale lines assayed by 11 restriction endonucleases with 38 different sites in the mtDNA cleavage map. The differentiation of the Canary Islands populations (delta = 0.0119) compared with the mean among all the other continental and insular populations (delta = 0.0002) is striking. Both the great divergence among Canary Islands nucleomorphs (delta = 0.021) compared with the maximum nucleomorph distance in all other populations (delta = 0.017) and the abundance of endemic nucleomorphs (11) on the Canary Islands (50% of the total number of different nucleomorphs found in the entire distribution area) suggest that this molecular differentiation most probably results from the very old age of the Canary Islands populations rather than from drift and founder effects.
Phase II study of weekly paclitaxel plus 5-fluorouracil in patients with unresectable advanced or recurrent gastric cancer
Authors: M. Ninomiya, K. Kondo, H. Kojima, K. Matsuo, N. Hirabayashi, S. Nakamura, S. Kawamura, M. Kobayashi, H. Konno, J. Sakamoto
Journal: Journal of Clinical Oncology (2005)

4075 Background: We conducted a phase I study on the paclitaxel (PTX) and 5-fluorouracil (5-FU) combination therapy in 18 patients with unresectable advanced or recurrent gastric cancer. The recommended dose was set at 600 mg/m2 for 5-FU and 80 mg/m2 for PTX as a result of that study. The present phase II multicenter cooperative study was conducted in 22 medical institutions using these doses from March 2003 to March 2004. Methods: Patients with unresectable advanced or recurrent gastric cancer with ECOG PS2 or better performance status were enrolled. The primary endpoint of this study was response rate. However, patients without measurable lesions were also enrolled, and the safety, overall survival, and QOL were evaluated. 5-FU was administered at 600 mg/m2 by 24-hr continuous infusion from days 1 through 5 and PTX at 80 mg/m2 by infusion on days 8, 15 and 22. This treatment was repeated every 4 weeks as long as possible. The response was evaluated according to the RECIST. Results: A total of 88 patients including the targeted 65 with measurable lesions were enrolled. The median age was 63 (range, 33–75). Sixty-six were males and 22 females. The performance status was 0/1/2/3 in 50/30/7/1 patients, respectively. Thirty- three patients had previous chemotherapy. The response rate was 35% with 2 CRs (3.3%) and 19 PRs (31.7%) in 60 evaluable patients. The median survival time was 375 days and the one-year survival rate 47.5% in all patients including those without measurable lesions. The incidence of hematological toxicities was 9.8% for G3/4 leukopenia, 17.1% for neutropenia, and 13.4%, for decreases in hemoglobin. Among non-hematological toxicities the incidence of G2 alopecia was 35.4%, but the incidence of GI toxicities was extremely low. Patients and received a median of 4 cycles (range, 1–15); 46.6% 4 or more cycles, and 20.5% 6 or more cycles. The compliance with this regimen was fairly good. Conclusions: The combination of weekly PTX and 5-FU is effective and well tolerated in advanced or recurrent gastric cancer and it is expected to contribute to better QOL and prognosis. No significant financial relationships to disclose.
Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC)
Authors: H. Kaur, P. Silverman, D. Singh, B. W. Cooper, P. Fu, S. Krishnamurthi, S. Remick, B. Overmoyer
Journal: Journal of Clinical Oncology (2006)

10623 Background: Single agent weekly docetaxel (D) is an active agent in the treatment of MBC with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR), and is overexpressed in 30–40% of breast cancers. EGFR inhibition by erlotinib (E) and its possible modulation of growth factor synthesis by breast cancer (BC) cells is an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent &amp;/or MBC. Methods: Adult patients (pts) with histologically confirmed BC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D [35 mg/m 2 iv infusion weekly x 3 q4wks] and E 150 mg/d uninterrupted (D+E). E was to be continued in 4 week cycles after maximum tumor response or disease stabilization [following a minimum of 6 cycles of D+E]. The overall survival (OS) was estimated by Kaplan-Meier method. Results: 31of 40 planned female pts were enrolled between 12/02 and 9/05. Median age 52 years, range: 29–79. The median number of cycles of D +E received was 4, (range 1–9) and of E following D+E was 4 (range 1–29). The first 26 pts received planned D dose of 35mg/m 2 . Because of non-hematologic toxicity, trial was subsequently modified to start D at 30mg/m 2 .11/31 (36%) were not evaluable due to toxicity. Hematologic grade 3 or 4 toxicity was seen in 45% cases. Principal non-hematologic grade 3–4 toxicities included nausea, diarrhea, and constitutional symptoms seen in 30% of the pts. 4/9 pts receiving E after D+E experienced hematologic, hepatic, constitiutional, and eye (1 each) grade 3 toxicity only. Best clinical response in the 20 evaluable pts included; PR 11(55%), SD 7 (35%), PD 2 (10%). OS (n = 31) was 71% at 12mos, 42% at 24 mos with median OS 23 mos. Conclusions: Combination therapy of advanced breast cancer with Docetaxel and Erlotinib showed promising activity with favorable response compared to other studies. The combination is associated with moderate to severe hematological and non-hematological toxicities. Randomized trials are warranted to further investivate the efficacy of this combination compared to single agent Docetaxel. (Support: Sanofi-Aventis &amp; Genentech.) [Table: see text]
Phase I trial of bevacizumab (BV) with concurrent radiotherapy (RT) and capecitabine (CAP) in locally advanced pancreatic adenocarcinoma (PA)
Authors: C. H. Crane, L. M. Ellis, J. L. Abbruzzese, E. B. Douglas, X. Henry, L. Ho, E. P. Tamm, N. Chaan, M. O’Reilly, R. A. Wolff
Journal: Journal of Clinical Oncology (2005)

4033 Background: Pancreatic cancers are resistant to RT. Vascular endothelial growth factor (VEGF) is overexpressed in many tumor types incuding PA. In vivo studies have shown that neutralizing VEGF activity can overcome radioresistance. Methods: Eligible patients for this phase I dose escalation trial had locally advanced, inoperable PA (AJCC 2002 T4, n=45), were inoperable based on pre-referral surgical exploration (T3, n=2) or medical comorbidity (n=1). Prior chemotherapy was allowed (n=25). An initial dose of BV (5 mg/kg IV) was administered 2 weeks prior to RT and every 2 weeks thereafter in successive cohorts of patients (12 patients each at 2.5, 5, 7.5, and 10 mg/kg) during RT (50.4 Gy to the primary tumor with capecitabine [650 mg/m2 PO BID (n = 6); 825 mg/m2 for the remaining patients]. Weekend doses of CAP were omitted in the final 12 patients. BV was continued (5 mg/kg IV q 2 wks) after RT until progression. Results: The worst acute gastrointestinal toxicity was grade 2 in 43% and grade 3 in 5% of patients. Two patients (5%) developed grade 3 hematologic toxicity and 24% developed grade 2 hand and foot syndrome. All patients completed RT and concurrent BV; (43%) of patients had at least a protocol-specified 25% dose reduction of CAP due to toxicity. Three patients had tumor-associated duodenal ulceration with bleeding [3, 10 (fatal), and 20 weeks after RT], and one had a contained duodenal perforation 10 weeks after RT). Primary tumor response: 9 of 41 evaluable had confirmed partial response (22% PR), 7 (17%) had minor response, 24 (59%) had stable disease and 2 (5%) had progressive disease. PR lasted until distant progression (median 6.2 months). Overall, only 5 patients have had local progression. Three patients have safely undergone pancreaticoduodenectomy. Median, 1 yr and 18 mo actuarial survival estimates were 15.7, 65% and 42% from the start of any therapy and 11.6, 45% and 29% from protocol entry. Conclusions: The addition of BV did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiation regimen. Preliminary efficacy results are encouraging. Multiinstitutional studies are planned (RTOG PA 0411 and ACOSOG Z5041). Supported by Genentech Inc. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Labs Genentech
Mistletoe extract/gemcitabine combination treatment: An interim report from the NCCAM/NCI phase I study in patients with advanced solid tumors
Authors: P. J. Mansky, D. B. Wallerstedt, B. P. Monahan, C. Lee, S. M. Swain, R. Evande, M. R. Blackman, J. Grem
Journal: Journal of Clinical Oncology (2005)

3098 Background: European Mistletoe (viscum album L.) extracts (ME) are used in varying doses and schedules as herbal adjunct treatment for solid tumors in Europe. Clinical efficacy remains controversial. Controlled data on safety, toxicity and drug interactions are lacking. Methods: Subjects with stage IV cancer (average age 51 years; breast 5, pancreas 4, colorectal 3, NSCLC 4) enrolled on a 2 stage dose escalation phase I trial of toxicity profile, dose limiting toxicity (DLT), MTD, and gemcitabine (GEM) pharmacokinetics (with and without ME) on s.c.qd ME (HELIXOR A, Helixor GmbH, KG, Rosenfeld, Germany) combined with GEM 750mg/m2i.v. on a weekly x 2 q 21d schedule for 3 cycles. We report on stage I (fixed dose GEM). Starting target ME dose level was 20mg (n=3), with escalations to 50 (n=3), 100 (n=3), 200 (n=5), and 250 mg (n=2). DLT for GEM is neutropenia. GEM and 2’,2’-difluorodeoxyuridine (dFdU) plasma concentrations (Cp) at baseline and week 8 (stable ME dose for 7 days) were determined by HPLC with UV detection o 12 subjects who completed 3 cycles (ME dose 20–200mg). The area under the curve (AUC) was determined using WinNonLin version 4.0. This project was approved by the Navy Clinical Investigation Program Project Number: 02–074 Results: No ME DLT was observed. Ten ME related grade 2 adverse events (AE, injection site reaction 4, flu-like syndrome 4, other local reaction 2), 30 grade 3 GEM-related AE (lymphopenia 12, neutropenia/low WBC 10, thrombocytopenia 2, nausea/vomiting 2, other 4) and 1 GEM related grade 4 lymphopenia were observed. Median baseline and week 8 AUC (664/670 min*nmol/ml, p=0.97) and Cp (47.7/49.7 nmol/ml, p=0.85) of GEM and dFdU (AUC 1038/1099 min*nmol/ml, p= 0.46, Cp 75.7/84 nmol/ml, p=0.67) were equivalent (signed rank test). 1038 of 1059 scheduled ME doses were given (compliance 98.2%). Tow subjects had partial clinical responses (PR) by RECIST (pancreas 1, NSCLC 1) and four subjects had stable disease > 18 wks (pancreas 1, NSCLC 2, rectal 1). Conclusions: The ME/GEM combination has been well tolerated. GEM Cp during infusion was unaffected by ME. Two subjects had a PR. Stage II (GEM dose escalation) will determine if addition of ME alters GEM toxicities and MTD. No significant financial relationships to disclose.
Phase II study of meloxicam with carboplatin plus docetaxel in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
Authors: T. Ishida, K. Kanazawa, H. Oizumi, H. Yokouchi, K. Yamazaki, K. Akie, N. Sukoh, M. Harada, M. Munakata, H. Isobe
Journal: Journal of Clinical Oncology (2007)

18121 Background: Preclinical and clinical studies showed that selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib or rofecoxib) might improve efficacy of treatment of advanced NSCLC. Meloxicam is a non-coxib, non-steroidal anti-inflammatory drug (NSAID), and selectively inhibits COX-2. Comparing with coxibs, meloxicam shows less cardiovascular toxicity; however, anti-tumor efficacy has not been proved in clinical settings. Methods: Eligibility criteria included stage IIIB/IV histologically or cytologically confirmed NSCLC, no prior chemotherapy, no current use of NSAIDs, PS = 0–1, and no urgent symptoms. Patients received oral meloxicam (150 mg) daily, and carboplatin (AUC 5) plus docetaxel (60 mg/m 2 ) day 1 every 3 weeks. Treatment was continued until disease progression or toxicity. The primary endpoint was anti-tumor effect, with secondary endpoints including the safety and time to progression. Calculated sample size was 45 patients (Simon’s two-stage minimax design). Results: From April 2005 to July 2006, a total of 50 patients (33 males/17 females, median age, 65 years) were accrued and 48 patients were eligible. Partial response was 40% (95% CI 24–56%), stable disease was 29% (95% CI 14–44%), and 23% had progressive disease. Grade 3/4 hematologic events included leukopenia (81%), neutropenia (96%), and thrombocytopenia (8%). Grade 3/4 non-hematologic events included hyponatremia (6%), anorexia (6%), fatigue (2%), and neuropathy (2%). Febrile neutropenia occurred in 2 patients, and one patient developed pneumonia. Conclusions: Meloxicam added to carboplatin plus docetaxel demonstrated acceptable tolerability with encouraging activity in advanced NSCLC patients. No significant financial relationships to disclose.
Benefits of dexrazoxane in female patients with stage II breast cancer treated with anthracycline-based adjuvant chemotherapy
Authors: I. I. Schnirer
Journal: Journal of Clinical Oncology (2009)

e11626 Background: In Israel, the majority of patients receiving doxorubicin (A) are treated with dexrazoxan (D). A retro-active study was carried out on cardiac effects of A and D on female patients receiving adjuvant chemotherapy for Stage 2 breast cancer. Methods: 34 newly-diagnosed chemotherapy-naïve female patients with Stage 2 breast cancer, received anthracycline-based chemotherapy treatment A with D ± Herceptin (HER). Cardiotoxicity was assessed by echo-cardiograph pre- and post- treatment, and thereafter every 3 months for a period of 2 years, and was defined by presence of CHF or a reduction in resting LVEF to &lt;45% or to ≥15% below baseline echo-cardiograph. Results: 34 patients were eligible for assessment. The mean age was 52, ranging from 24 to 78. Chemotherapy regimen consisted of 4 cycles of A + cyclophosphamide + D ± HER (HER treatment over a period of one year) + paclitaxel (PAC) (12 courses). Of the 34 patients, 7 (20.5%) were Her2 new positive. 17 patients (50%) were estrogen (ER)/progesterone (PR) positive. 9 patients (26.4%) were triple negative. 2 of the Her2 new positive patients were also ER/PR positive. Average m 2 per study population was 1.63 (mean range being 1.39 - 1.87). Average A dosage was 60mg/m 2 and mean D dose was 391.2mg (between 333.6mg and 448.8mg). Ratio of A to D was 1:10. Echo-cardiograph pre- treatment ranged from 80% - 60%, a normal range according to the New York Health Association (NYHA). Post-treatment echo-cardiograph ranged from 70% - 45%. One patient from HER positive group (generally experiencing increased cardiotoxicity by 4%) showed decrease in LVEF by 14.3% (14.2% of Her2 new patients). Remaining patients showed no change. One patient from ER/PR positive group experienced a 12.3% reduction in LVEF, representing 5.88% of the ER/PR patients. Remaining ER/PR positive patients remained unchanged, with one patient showing increased LVEF from 60% to 70%. The triple negative patient showed no change in their echo- cardiograph results. Conclusions: This study confirms that no scientific or clinical-based evidence was found of anthracycline- based cardiotoxicity following administration of A plus D, in accordance with published medical evidence. D should be a standard of care for anthracycline-based chemotherapy. No significant financial relationships to disclose.