tbuckley/cabot-search huggingface dataset:
Phase I study of irinotecan (CPT-11) and capecitabine in combination with concurrent radiotherapy for locally advanced rectal cancer
Authors: R. Hofheinz, B. Von Gerstenberg, F. Wenz, U. Gnad-Vogt, U. Tiefenbacher, S. Saussele, S. Kreil, A. Hochhaus, F. Willeke
Journal: Journal of Clinical Oncology (2004)

3696 Background: Several neoadjuvant radiochemotherapy protocols using simultaneous CPT-11 and infusional 5-fluorouracil (5-FU) have resulted in pathological complete response rates (pCR) of about 25% in the treatment of locally advanced rectal cancer. Capecitabine is known for its radiosensitizing properties. Moreover, it mimics the pharmacokinetics of infusional 5-FU. Thereferore, it seemed rationale to combine capecitabine with CPT-11. Methods: We conducted a phase I study applying weekly CPT-11 50mg/m2 (one hour before radiation on days 1, 8, 15, 22, 29) and increasing doses of capecitabine (days 1–35; dose level [DL] I: 1000mg/m2, II: 1250mg/m2, III: 1500mg/m2) to cohorts of at least three patients per DL. The radiation dose was 50.4 Gy (45 Gy + 5.4 Gy). The purpose of the study was to establish the recommended dose (RD) of capecitabine in combination with CPT-11 and radiotherapy. Surgery was performed within 4–6 weeks after the completion of chemoradiation. Patients (pts) with primary rectal cancer clinical stage uT3/N+ or uT4 Nx were eligible. DLT was defined as (NCI-CTC version 2.0) hematological toxicity grade 4, febrile neutropenia, diarrhea grade 3, organ toxicities grade 3 with the exception of renal toxicity grade 2. Results: 19 pts have been included: 16 male, 3 female; median age 62 years (range 34–78); median ECOG PS 1. uT3 n=18, uT4 n=1. N positive n=16. On DL I no DLT occurred. On DL II 3 out of 7 pts experienced DLT (diarrhea grade 3). Therefore, dose level II was determined as maximum tolerated dose. A total of 12 pts was treated on DL I: Median relative dose intensity was 100% for both drugs. No grade 3–4 toxicity was observed. Toxicities were (grade 1–2): Leucopenia 50% - 8%. Diarrhea 33% - 42%, nausea/vomiting 33% - 25%, radiodermatitis 33% - 33%. All 19 pts have undergone surgery. pCR was observed in 4 pts and another 5 pts had microfoci (MF) of residual tumor. Conclusion: Preoperative chemoradiation with CPT-11 and capecitabine is a feasible and tolerable treatment. The pCR and MF rates and the toxicity profile observed in our series are comparable to those published for infusional 5-FU and CPT-11 schedules. No significant financial relationships to disclose.
Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis
Authors: Nicola Fossati, Nazareno Suardi, Giorgio Gandaglia, Carlo A. Bravi, Matteo Soligo, R. Jeffrey Karnes, Shahrokh Shariat, Antonino Battaglia, Wouter Everaerts, Steven Joniau, Hendrik Van Poppel, Nieroshan Rajarubendra, Inderbir S. Gill, Alessandro Larcher, Alexander Mottrie, Maximilian Schmautz, Axel Heidenreich, Almut Kalz, Daniar Osmonov, Klaus-Peter Juenemann, Annika Herlemann, Christian Gratzke, Christian Stief, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2018)
Invasive renal pelvis transitional cell carcinoma
Authors: F. Freiha, S. Srinivas
Journal: Journal of Clinical Oncology (2004)

4694 Background: Upper tract tumors of the renal pelvis and ureter represent a small proportion of patients with transitional cell carcinoma. The natural history of this disease is poorly studied due to the rarity and small numbers. We report our experience with invasive renal pelvis and proximal ureter transitional cell carcinoma. Methods: All patients seen at our institution between 1995 and 2003 with renal pelvis and proximal ureter who had adequate follow up were selected. Of the 37 patients, 13 were ineligible (6= distal ureters; 3=non invasive cancers; 1=urethral cancer; 1=co existing lung cancer; 2=no follow up). Results: The median age was 72(47–92), 2/3 of the patients were men; renal pelvis was the primary site in 21, upper ureter in 3; 13 (54%) were smokers; ten patients (42%)had bladder tumors either preceding the renal pelvis tumor or after; six (25%) of the patients had distant metastases; ten (42%) had nodal metastases;The median overall survival was 27 months. The overall survival of patients with and without distant metastases was 5 months and 50 months respectively. (P=. 0004). In those patients without nodal metastases, the T stage determined prognosis. Overall survival for patients with T3/4 was 18 months versus 75 months for T1/2 patients (P=. 003). Adjuvant chemotherapy in this small series did not have an impact on survival. The overall survival of patients with distant metastases in bladder cancer varies from 9 months to 33 months depending on the performance status and visceral metastases. Conclusions: The median survival of patients with metastatic renal pelvis and upper tract tumors is worse than bladder cancer. Early detection and adjuvant chemotherapy may have an impact and should be studied in larger number of patients. No significant financial relationships to disclose.
Epirubicin-carboplatin-capecitabine (ECarboX) in relapsed ovarian cancer: A phase I/II trial
Authors: R. Hubner, T. Ahmad, A. Rigg, S. Kaye, I. Gibbens, C. Keyzor, A. Prouse, M. Gore
Journal: Journal of Clinical Oncology (2004)

5109 Background: We have previously shown the combination of epirubicin, cisplatin, and prolonged infusional 5-fluorouracil (5-FU) is active in relapsed epithelial ovarian cancer (EOC). Capecitabine (Xeloda, X) is an orally bioavailable tumour selective fluoropyrimidine, it has proven efficacy and is more convenient than infusional 5-FU. We have performed a phase I/II study of ECarboX in relapsed EOC. Methods: Patients (pts) with relapsed EOC with an interval of at least 6 months from platinum-based first line treatment, received bolus iv epirubicin 50mg/m2 and iv carboplatin AUC 5 on day 1, and capecitabine either 750mg/m2 (level 1) or 1000mg/m2 (level 2) daily in two divided doses throughout a 21-day cycle, or 1000mg/m2 daily for days 1–14 of a 21-day cycle (level 3). Pts were planned to receive 6 cycles. The primary endpoint was the maximum tolerated dose (MTD) of ECarboX. Tumour response was a secondary endpoint. Results: Eleven pts have entered the study and eight have received ≥3 cycles of ECarboX and are evaluable. At level 1 two pts completed 6 cycles and one pt 4 cycles of treatment. Seven cycles were delayed, and 50% dose reductions in epirubicin and capecitabine were required in two pts: one pt had recurrent grade 3 neutropenia, the other had grade 3 neutropenia, lethargy and diarrhoea, and was subsequently withdrawn for prolonged (>2 week) grade 2 neutropenia despite dose reduction. At level 2 four out of five pts completed 6 cycles, the fifth received 2 cycles. There were 11 treatment delays: 2 pts had 25% dose reductions and 1 pt was withdrawn from the study due to prolonged grade 3 neutropenia. Four pts experienced grade ≥2 haematological toxicity and one pt grade 3 lethargy. At level 3, three pts have received 2 cycles each, one cycle has been delayed. Six pts have obtained a partial or complete response and one has stable disease. Only one pt progressed. Conclusions: ECarboX results in haematological toxicity. The MTD was level 2, capecitabine 1000mg/m2 for 21 days of a 21-day cycle. Capecitabine on days 1–14 of a 21-day cycle is likely to be better tolerated. As expected, ECarboX is highly active in relapsed EOC. No significant financial relationships to disclose.
High pathological response rate in esophageal cancer after neoadjuvant radiotherapy (RT) and concomitant weekly chemotherapy with dose escalating of docetaxel (D)
Authors: F. Pasini, G. De Manzoni, E. Durante, C. Griso, A. Grandinetti, M. Gabbani, C. Pedrazzani, S. Maluta, A. Bonetti, G. L. Cetto
Journal: Journal of Clinical Oncology (2004)

4059 Background: dose-dense therapy should allow more frequent delivery of moderate doses over a short period with greater efficacy and lower toxicity than standard doses every 3 weeks. This neodjuvant phase I protocol was based on weekly D and cisplatin (P), continuous infusion (c.i.) of 5-FU and concomitant RT. The doses of D and RT were progressively escalated. Aims were pathological response rate and toxicity. Methods: from Oct 99 to Oct 03, 41 non metastatic pts (31 adenocarcinomas) were enrolled; median age was 61 yrs (47–76). Step 1: D and P 20 mg/m2 d 1,8,15 plus 5-FU 150 mg/m2 c.i. d 1–21. After one week rest, the same cycle was repeated at days 28, 35, 42 concurrently with RT (40 Gy). Step 2: D and P 25 mg/m2; 5-FU 180 mg/m2 days 1–21. Step 3: 5-FU prolonged to four weeks during RT (150 mg/m2 days 28–56). Step 4: D and P 25 mg/m2 added at day 49. Step 5: RT increased to 50 Gy. Step 6: D 30 mg/m2. Step 7: D 35 and P 25 mg/m2 added at day 56 and 5-FU prolonged to 5 weeks. Surgery was performed 4 to 6 weeks after completion of RT. Results: all the pts, but one, completed the planned chemo-radiation. The cumulative doses reached in step 7 were: D 280 mg/m2, C 200 mg/m2, 5-FU 9030 mg/m2, RT 50 Gy. Transient grade 3–4 hematological toxicity occurred in 1/123 cycles of the first phase and in 3/144 cycles of the concomitant phase. The worst non-hematological toxicities during the concomitant phase were of grade 2: nausea in 12/144 (8%), asthenia in 8/144 (6%) and esophagite in 5/144 (4%) of the cycles, respectively. Pathological findings: complete response [pT0 (or residual microfoci) pN0] 46% (19 pts), PR 27% (11 pts), stable disease 7% (3 pts), no response 20% (8 pts); pT0 (or residual microfoci) 25 pts (61%), pN0 21 pts (51%), pN1 6 pts (15%). Conclusions: i) this weekly protocol with concomitant RT was feasible ii) a substantial pathological response rate (46%) has been achieved iii) the doses of the drugs are the highest so far reported in concomitance with RT iv) the weekly schedule has modified the toxicity profile allowing concomitant chemo-RT at doses otherwise impossible with three weeks schedules including standard doses of docetaxel. No significant financial relationships to disclose.
Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: H. Katori, M. Tsukuda, J. Ishitoya, Y. Mikami, H. Matsuda, Y. Tanigaki, C. Horiuchi, Y. Ikeda, M. Ono, S. Hirose
Journal: Journal of Clinical Oncology (2004)

5560 Background: The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods: Nineteen patients with previously untreated stage III-IV SCCHN were included in this trial. Patients received 2 cycles of chemotherapy repeated every 4 weeks. Starting doses (dose level 1) were docetaxel 60 mg/m2, cisplatin 70 mg/m2, and 5-day continuous infusion 5-FU 600 mg/m2/day. Radiation was targeted to begin on the starting day of chemotherapy, day1. The total radiation dose to the primary tumor site and neck lymph nodes was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. Results: Maximum-tolerated dose (MTD) was that: docetaxel 60 mg/m2, cisplatin 60 mg/m2, and 5-fluorouracil 600 mg/m2/day. The main toxicities were mucositis (Grade3 and 4, 79%), leukocytopenia (Grade 3 and 4, 53%), neutropenia (Grade 3 and 4, 42%), anemia (Grade3, 16%), liver dysfunction (Grade3, 11%) and renal dysfunction (Grade2, 11%). The overall response rate was 100% including 84% complete responses (CR). Conclusions: This concurrent chemoradiotherapy with TPF was safe and well tolerated. The high complete response rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients. No significant financial relationships to disclose.
Stakeholder perspectives on the use of telehealth to improve ambulatory care for chemotherapy patients in a large urban cancer centre.
Authors: Samik Doshi, Jeremy Chad, Karin Archer-Myles, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2017)

86 Background: Chemotherapy outpatients are often left in vulnerable positions without direct access to their providers between appointments, which can lead to Emergency Department (ED) visits to address side effects. Improved use of telehealth has been postulated in the literature as a potential low-cost tool to manage this problem. Our objective was to explore, as a case study, how telehealth can be optimized to provide better care to ambulatory chemotherapy patients. Methods: This study was done at Princess Margaret Cancer Centre in Toronto. Semi-structured interviews (n = 21) were conducted to elicit a broad set of perspectives on the feasibility and constraints of implementing new telehealth measures in the breast cancer (BC) clinic. Interviewees included hospital administrators (n = 3), nurse managers (n = 4), BC nurses (n = 3), BC physicians (n = 2), one non-BC nurse, one pharmacist, BC patients (n = 4), and telehealth and technology experts (n = 3). Transcripts were reviewed separately by each author and themes were extracted using content analysis. Key learnings were established based on stakeholder agreement and theme novelty. Results: Provider-initiated proactive calling of chemotherapy patients was felt to bethe most valuable and feasible potential change according to all stakeholders. A number of key considerations emerged regarding the creation of a successful proactive calling system: 1) calls should address symptoms that are predictable, regimen-specific, and most likely to result in ED visits; 2) patients most likely to benefit are those beginning chemotherapy, starting new drugs, or fitting certain high-needs criteria; 3) structured call questionnaires can be valuable, but must be flexible to best meet patient needs; 4) the caller’s expertise is more important than his or her familiarity with the patient; and 5) basic IT support systems are necessary for operationalization. Conclusions: Simple telehealth initiatives such as proactive calls can improve outpatient care for chemotherapy patients, and may reduce ED burden. This study provides key principles that should guide development and implementation of proactive calling programs at cancer care institutions.
Quality indicators for cervical cancer care in Japan.
Authors: Tomone Watanabe, Satoru Kamitani, Momoko Iwamoto, Takahiro Higashi
Journal: Journal of Clinical Oncology (2017)

219 Background: Although ensuring high-quality care has a central role in Japanese cancer policy, introduction of a system to evaluate quality is still underway. With the goal of establishing a sustainable measurement system, this study assesses adherence to quality indicators (QIs) as an index for evaluating the quality of care for cervical cancer patients in Japan. Methods: Ten measurable QIs were devised by an expert committee using the modified Delphi method. Adherence to each QI was calculated by using hospital cancer registry data of patients diagnosed during 2013 and claims data between October 1, 2012, and December 31, 2014. Using registry-linked claims data across 281 hospitals, we measured 3 QIs on treatment for CIN3, 3 QIs on stage III or IVA, and 1 QI on stage IVB, respectively. We also measured 1 QI on examination of cancer spread and 1 QI on brachytherapy. Results: Data for 11,925 cervical cancer patients were analyzed. Patients’ mean age was 45.4 years (SD: 15.1). Among the QIs, use of platinum-based chemotherapy among stage IVB patients (99.1%), total hysterectomy as the last treatment among intraepithelial adenocarcinoma patients over age 44 years (87.7%), and selection of cisplatin-based regimen for concurrent chemo-radiation therapy (CCRT) (81.2%) to stage III/IVA diseases marked high adherence. In contrast, evaluation with cystoscope or proctoscope among stage IVA patients (32.4%) and use of CCRT as the initial treatment for stage III or IVA patients (49.5%) had relatively low adherence. Conclusions: The observed variation in adherence to QIs could demonstrate the provision of unstandardized care across Japan. Feedback on the results and continued monitoring are necessary to improve the quality of cervical cancer care.
Clinical, pathologic, and radiologic response in patients with neurofibromatosis type 2 (NF2) undergoing bevacizumab treatment.
Authors: Niamh Coleman, Megan Greally, Lynda O' Riordan, Teresa Doyle, Oscar S. Breathnach, William Grogan
Journal: Journal of Clinical Oncology (2013)

e13049 Background: NF2 is a rare inherited genetic condition characterized by multiple "benign" tumors in the peripheral and central nervous system. Profound hearing loss as a result of bilateral vestibular schwannomas is a major debilitating complication with a profound effect on quality of life. Vascular endothelial growth factor (VEGF) has been shown to be produced by vestibular schwannoma tumor cells. Bevacizumab, a humanized monoclonal antibody against VEGF, has been proposed as a treatment for patients with advanced NF2, who are poor candidates for surgery and radiation therapy. The aim of this study was to investigate and assess the benefit of treatment with bevacizumab in the treatment of patients with advanced NF2. Methods: Five patients with inoperable NF2 were assessed prospectively from 03/12-01/13. Pathological assessment of tissue for vascularity was performed in each of the patients’ tissue. Objective assessments, including audiogram and MRI brain, were performed pre- and during therapy. Qualitative assessments were undertaken to assess subjective response to treatment. Results: We identified 5 patients with advanced NF2 [n=5], 3 female 2 male with a median age 40 years [range 28 – 52] as outlined in the Table. Tumor-volume reduction of &gt;20% was noted on MRI imaging in the vestibular schwannomas of 2 patients. 2 patients showed objective improvement on audiogram with subjective hearing improvement also noted. Other subjective responses noted include increased energy levels, less headaches, better concentration. Conclusions: Bevacizumab treatment in patients with advanced NF2 resulted in some symptomatic improvement, tumour shrinkage, improvement in disability. Patients with vestibular schwannomas appeared to receive the most benefit, and so in terms of palliation, the benefits may be most significant in patients with specific disabilities, such as hearing loss. [Table: see text]
Phase II study of low dose CPT-11 administered three times weekly in fluorouracil refractory patients with metastatic colorectal cancer
Authors: E. Shinozaki, N. Mizunuma, E. Nagasaki, N. Horikoshi, T. Muto, Y. Takahashi, K. Hatake
Journal: Journal of Clinical Oncology (2004)

3719 Background: CPT-11 is one of the most active agent for colorectal cancer and usually used as 2nd line of single agent after fluorouracil-based chemotherapy. Because oxaliplatin has not been approved yet in Japan. Although biweekly schedule is common in Japan, it is difficult to undergo strictly along its schedule due to the toxicity such as diarrhea or neutropenia. A phase II study of CPT-11 administered three times weekly in patients with metastatic colorectal cancer was performed, decreasing adverse effect and increasing antitumor effect. Methods: CPT-11 was administered as 25mg/m2 three times weekly by intravenous infusion. The treatment schedule was repeated every two weeks (one cycle), which was repeated until there was evidence of disease progression. 27 patients were enrolled in this study and evaluated for toxicity and response. Results:The response rate was 26.9% (7PR, 6MR, 5NC, 6PD, 2NE). Progression free survival was 21.0 weeks (range 10.3 to 56.4 weeks). The major toxicities (grade 3,4) were diarrhea (30.8%), appetite loss (7.7%), neutropenia (11.5%). Conclusions: Low dose CPT-11 administered three times weekly showed substantial antitumor activity as a 2nd line single agent chemotherapy against metastatic colorectal cancer. Adverse events were generally well tolerated and less toxic than that of conventional dose of biweekly infusion except diarrhea. Low dose CPT-11 chemotherapy is considered to be a dose-dense therapy and be able to combine with other agents such as EGFR inhibitors in the future. No significant financial relationships to disclose.
Population PK/PD model for diflomotecan, a new E-ring modified camptothecin analogue, in patients of a phase I study
Authors: P. Principe, I. F. Troconiz, C. Segura, M. J. Garrido, J. M. Cendros, C. Peraire, R. Obach
Journal: Journal of Clinical Oncology (2004)

2046 Background: To develop a semimechanistic population PK/PD model of neutropenic effects of diflomotecan, to establish the concentration-effect relationship and to quantify the degree of interpatient variability. Methods: PK data were obtained from 24 patients with advanced cancer receiving diflomotecan as 20 min i.v. infusion every 3 weeks at planned starting doses of 2, 4, 5 and 6 mg/m2. The number of cycles ranged from 1 to 7. Diflomotecan was measured in 258 plasma samples after the 1st administration. Neutrophil cell counts in peripheral blood were followed every 3–7 days for the entire course of the trial with a total of 505 counts. Population PK/PD analysis was done with NONMEM. Dose, demographic and biochemical variables were tested as covariates. Results: Plasma levels-time data were described with a 3-compartment model and first order elimination. Typical estimates of distribution volumes were 41.5, 39.2 and 12.8 L for central (Vc), shallow (VP1) and deep (VP2) compartments, respectively. Body surface area (BSA) and gender were the only covariates included in the model. Vc increased linearly with BSA: Vc = 41.5 x (BSA/1.85), and VP1 was lower in females (29.5 vs 48.8 L). Simulation analysis showed that neither covariate exerts a clinically relevant influence. The typical value of CL was 21.6 L/h. Interpatient variability was 52% for Vc and 51% for CL. The time-course of neutrophil cell counts was described by means of a semimechanistic model including self-renewal, maturation, homeostatic regulation processes and drug effects (Friberg et al, 2002, J. Clin. Oncol., 20:4713–4721). Values of 4.58 cells x 109/L, 5.38 days and 637.4 μM-1 (based on unbound concentrations) were estimated for Circ0 (baseline neutrophil counts), MTT (mean transit time) and slope (parameter related to the cytotoxic potential of the drug), respectively. Conclusions: The semimechanistic population PK/PD model described the time course of diflomotecan plasma concentrations and its haematological toxicity profiles appropriately. Consequently, this model may be used to predict the time-course of neutrophil cell count in future clinical studies. No significant financial relationships to disclose.