tbuckley/cabot-search huggingface dataset:
Duration of G-CSF therapy and risk of hospitalization for neutropenia or infection
Authors: D. Weycker, J. Hackett, J. Edelsberg, G. Oster, A. Glass
Journal: Journal of Clinical Oncology (2004)

6731 Background: Clinical trials have demonstrated that 10–12 days of granulocyte-colony-stimulating factor (G-CSF) prophylaxis is effective in reducing the risk of febrile neutropenia in patients receiving myelosuppressive chemotherapy. In clinical practice, however, many patients receive shorter courses of prophylaxis. The effectiveness of these shorter courses is unknown. Methods: Using a large US health-insurance claims database, we identified all adults with non-Hodgkin's lymphoma (NHL) who received myelosuppressive chemotherapy and G-CSF prophylaxis between 1998 and 2002; unique cycles of chemotherapy were identified. We then focused attention on all patient-cycles in which G-CSF was administered by cycle day 5 (“G-CSF prophylaxis”). Pooling all such cycles, we used a GEE (Generalized Estimating Equation) model (with a logistic link function) to examine the relationship between duration of G-CSF prophylaxis and risk of hospitalization for neutropenia or infection, adjusting for potential confounders. Results: Duration of G-CSF prophylaxis was <10 days (mean+/-SD, 6.6+/-3.3) in 77% of 336 patient-cycles during which G-CSF prophylaxis was administered. There were 31 hospitalizations for neutropenia or infection. Risk of hospitalization was significantly lower (OR: 0.81, p<0.01) with each additional dose of G-CSF, up to a maximum of 14 doses; patients receiving 5 doses of G-CSF, for example, were approximately 3 times (OR: 2.9, 95%CI 1.5–5.5) more likely to be hospitalized than those receiving 10 doses. A higher Charlson Index also was associated with a higher risk of hospitalization (OR: 1.25, p<0.01). Conclusions: Among NHL patients receiving G-CSF prophylaxis, risk of hospitalization is related to duration of therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc. Amgen, Inc.
Cetuximab added to docetaxel, cisplatin, 5-fluorouracil Induction chemotherapy (C-TPF) in patients with newly diagnosed locally advanced head and neck cancer: A phase I study
Authors: R. B. Tishler, M. R. Posner, L. J. Wirth, T. Balboni, R. Costello, L. Goguen, D. Annino, N. Livada, C. M. Norris, R. I. Haddad
Journal: Journal of Clinical Oncology (2008)

6001 Objective: Phase I study to determine the maximum tolerated dose (MTD) of 5-FU in the Docetaxel/Cisplatin/5-Fluorouracil (TPF) regimen (Posner et al, NEJM 2007) when combined with Cetuximab (C) for locally advanced squamous cell carcinoma of the head and neck. Material and Methods: Pts with previously untreated SCCHN were enrolled. The primary end point was to establish an MTD of 5-FU in this regimen. A standard dose escalation scheme of 5-FU was used. Three patients (pts) enrolled on each cohort. The dose escalated to the next level if no DLT was encountered. 5-FU cohorts were 700, 850 and 1,000 mg/m2/d for 4 days via continuous infusion. The doses for C, T and E are 100mg/ms2, 75 mg/m2 and 400/250 mg/m2 respectively. TPF was given every three weeks for three cycles and C was given weekly for a total of nine weeks, starting on day 1 of TPF. After C-TPF, all pts received concurrent chemoradiotherapy. Results: A total of 19 pts are enrolled. All pts had stage 4 disease. (T4, n=8, N3, n=7). Median age 57, 17 males, 14 oropharynx. 19 PS 0. No DLT was encountered on dose levels 1 and 2. At dose level 3 one DLT was encountered (Febrile neutropenia) and three more pts were enrolled with no DLT. In the expansion cohort at the MTD, two pts had grade 4 GI toxicity consisting of abdominal enteritis requiring hospitalization and blood transfusion. Decision was made to decrease the 5-FU to dose level 2 of 850 mg/m2. Fifteen pts have completed all three cycles of C-TPF at this time. The average weeks of cetuximab delivered is 7 of 9 planned; Reasons for holding cetuximab are nail fissuring (Grade (G) 3, one pt, G 2, 7 pts). Other toxicities encountered are: G 4 neutropenia (5 pts), G4 thrombocytopenia (1 pt), febrile neutropenia (3 pts), skin rash (G 2, 10 pts, G3, one pt). After all therapy including chemoradiotherapy 11 pts have CR and 1 PD, 7 too early. Conclusion: C-TPF appears to be safe and feasible as given in this study. GI toxicity appears to be the major combined DLT. Skin rash is frequent and limits C dosing. Reducing the 5-FU in TPF to 850 mg/m2 reduces GI toxicity. The average number of weeks of C delivered per patient is 7/9 weeks. The study continues at the declared MTD, dose level 2 of 5 FU of 850 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, sanofi-aventis
Low cardiotoxicity of nonpegylated liposomal doxorubicin (NPLD) in patients (pts) with metastatic breast cancer (MBC) previously exposed to 360 mg/m<sup>2</sup> of doxorubicin (D).
Authors: E. Muñoz, J. M. Perez-Garcia, C. Saura, M. Vidal, G. Sanchez-Olle, M. Bellet, P. Gomez, S. Di Cosimo, J. Baselga, J. Cortes
Journal: Journal of Clinical Oncology (2010)

1112 Background: In pts with MBC, retreatment with chemotherapy agents given previously in the early disease setting is a valid therapeutic option. Re-introduction of anthracyclines is limited by the risk of accumulative cardiotoxicity. Since NPLD is less cardiotoxic, administration of NLPD could be a potential strategy to re-introduce anthracyclines in MBC. In order to explore this hypothesis, we have analyzed the cardiotoxicity NPLD-containing regimes in pts with MBC previously exposed to D 360 mg/m2. Methods: Pts had PS 0-2, basal left ventricular ejection fraction (LVEF) >50%, adequate organ function, and prior exposure of D in the (neo)adjuvant setting at a dose of 360 mg/m2. No prior liposomal anthracyclines were allowed. LVEF was measured before initiating treatment with NPLD and at least at the time of treatment discontinuation. Cardiac events were defined as type A in case of signs and/or symptoms of congestive heart failure plus grade 3/4 LVEF decline; or type B including asymptomatic LVEF decline, defined as an absolute drop ≥10% resulting in a final LVEF <50%, any absolute drop >20%, or LVEF <40%. Results: From 2004 to 2009 32 MBC pts who had received prior D 360 mg/m2, have been treated with NPLD-based therapy. Median prior number of chemotherapies regimens were 4 (2-9). Median cumulative dose of NPLD was 258 mg/m2 (range, 60-480) and the median number of cycles was 4 (1-8). Median LVEF at baseline was 60% declining to 54% after NPLD treatment, with a median LVEF decline of 5.75% (p< 0.001). No Type A cardiac events were observed. Type B events occurred in 9 pts (28.1%) with a delay in treatment due to LVEF decline in 6 of them (66.7%). Median time to progression was 3.06 months (95% CI 2.19-3.92) and median overall survival was 11.4 months (95% CI 8.12-13.96). Conclusions: NPLD administration in patients previously treated with D 360mg/m2 results in low cardiac toxicity and absence of type A (symptomatic) events. Our results are similar to that previously reported by our group in pts exposed to D at doses lower than 360 mg/m2 and suggest that NPLD is a valid option in pts with advanced disease that have progressed to approved agents. No significant financial relationships to disclose.
In vivo molecular changes in patients (pts) with metastatic melanoma treated with EMD121974 (selective antagonist of avβ3 integrin)
Authors: R. W. Joseph, V. G. Prieto, N. Papadopolus, N. Papadopolus, A. Bedikian, A. D. Colevas, K. Kim
Journal: Journal of Clinical Oncology (2009)

9058 Background: αvβ3 integrin promotes the proliferation of tumor-associated endothelial ells and potentiates the survival of melanoma cells through activation of downstream kinases. Here we report the molecular changes of downstream kinases in tumors of pts with metastatic melanoma treated with cilengitide, a selective antagonist of αvβ3, in a phase II study. Methods: In this study, 26 pts were treated, and all tissues were embedded in OCT and immediately frozen in liquid nitrogen at -80° C until further analysis. Immunohistochemical staining was performed for the expression of αvβ3, pFAK, pERK1/2 and pAKT. Results: There were 1 pt with a partial response (PR) and 3 pts with stable disease (SD) in the study. All 26 pts had pre-treatment biopsies, and 18 underwent second biopsy on day 8. Adequate paired tumor samples were available in 16 pts for αvβ3, 11 pts for pAKT, and 9 pts for pERK1/2 and pFAK. Six (23%) of 26 pts had intratumoral expression of αvβ3 (defined as ≥25% of tumor cells stained positive) pre-treatment. The sole responder and 2 of 3 pts with SD did not express avβ3 at baseline. Cilengitide decreased the expression of αvβ3 (p = 0.04), but not the expression of the downstream kinases. The decreased expression of αvβ3 with treatment was correlated with the decrease in pERK1/2 expression (p = 0.03) but not with pAKT or pFAK. Conclusions: Although cilengitide decreased melanoma expression of αvβ3, its clinical efficacy was minimal in this study. These data suggest that the benefit of cilengitide in pts with disease control (PR+SD) was secondary to anti-angiogenic activity rather than direct anti-tumoral effect. Supported in part by NCI grant N01 CM-17003 and CA16672. [Table: see text] No significant financial relationships to disclose.
A phase I study of oxaliplatin (OX) in combination with bortezomib (B) in patients with advanced malignancy
Authors: R. Chang, A. Beric, L. F. Liebes, J. Wright, P. Ivy, B. Norwood, J. Escalon, F. M. Muggia, H. S. Hochster
Journal: Journal of Clinical Oncology (2005)

9678 Background: Proteasome inhibition has profound effects on cell cycle control and on the activation of transcription factors and anti-apoptotic signals such as NF-kB. It may potentiate DNA damage induced by platinum adducts. Our purpose was to study the safety and tolerability of the combination, particularly with respect to neurotoxicity. Patients and Methods: To identify the MTD and DLT of OX (d1, week 1 & 3) in combination with B (d1 & 4, week 1 & 3), at least 3 pts were treated at each level. Formal neurologic assessment of vibratory discrimination was done at baseline and monthly. Results: 17 pts with metastatic malignancies (gastric, bile duct, pancreatic, appendiceal, melanoma, ampulla of Vater, colon, and ovarian cystadenocarcinoma) without limit on prior therapies were accrued: males/females: 8/9; median age 56 yrs (35–74); ECOG PS 0/1/2: 7/10/0. Myelosuppression was minimal. Overall, 48.5 cycles of treatment (median/pt =2, range 0.5–8) were given. 3/145 (2%) treatments were delayed because of toxicity, and 2/145 (1.3%) were dose reduced. Formal neurologic testing showed consistent changes without relationship to clinical symptoms (additional data to be presented). Among 15 pts with measurable disease completing at least one cycle, there were 1 PR (GE junction), 5 SD (1 GE junction, 1 pancreas, 1 gastric, 2 ampullary) and 9 PD. One pt with GE junction adenocarcinoma (unresponsive to irinotecan/cisplatin), subsequently had PR to OX/B and went on to full resection. Conclusions: OX and B exhibit dose limiting cumulative neurotoxicity, more characteristic of symptoms attributable to B, such as ataxia and muscle fatigue, at B doses of 1.3 mg/m2 or greater. The addition of OX may potentiate these symptoms. Chronic tolerance will be explored at 85 OX and 1.0 B dose level. Supported by CA 16087 and CM-07003–74. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo
Hypertension and survival in unresectable metastatic colorectal cancer (mCRC) patients receiving first-line bevacizumab (BEV) and FOLFOX.
Authors: B. L. Burnette, A. Grothey
Journal: Journal of Clinical Oncology (2010)

e14066 Background: BEV combined with chemotherapy (CT) has shown to be efficacious for treatment of a variety of malignancies. A common toxicity of BEV is hypertension (HTN). Predictive markers for the efficacy of BEV have been largely elusive, but recent reports correlated HTN on BEV with better survival. We assessed the outcome of patients with unresectable mCRC in correlation with HTN on BEV at our institution. Methods: The pharmacy database was searched for patients with mCRC who received FOLFOX with BEV in the palliative first-line setting from 2/1/2004-6/1/2007. Exclusion criteria included: less than 3 doses of BEV, less than 4 doses of CT, resectable/potentially resectable, incomplete follow up, and history of metastectomy. Results: 12 patients with HTN on BEV and 24 patients without HTN were identified that met eligibility criteria. 3/12 patients with HTN toxicity and 8/24 patient without HTN toxicity had HTN at baseline. Patients with HTN had characteristics that included: mean age, 58.4 y; 6 M/6 F; mean cycles of first-line FOLFOX, 9.6; mean first-line BEV, 8.3. Patients without HTN had characteristics that included: mean age, 60.8 y; 11 M/13 F; mean cycles of first-line FOLFOX, 9.1; mean first-line BEV, 7.8. The two groups had similar disease burdens. Of the 12 patients with HTN 8 had a partial response (PR) and 4 had stable disease (SD). Of the 24 patients without HTN 6 had a PR, 8 had SD, and 10 had progression of disease. Overall survival was 31.8 mo in the HTN group and 17.7 mo in the non-HTN group. At the study conclusion, 3/12 HTN patients remained alive and receiving treatment and 1/12 patients remained alive under hospice care. No patients without HTN remained living at study conclusion. Conclusions: This small retrospective series with matched patients, suggests that patients who develop HTN while receiving first-line BEV with FOLFOX for unresectable mCRC may have improved outcome. HTN as a biomarker for efficacy of BEV warrants further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Bayer, Genentech
Induction chemotherapy with carboplatin and paclitaxel followed by radiotherapy and concurrent weekly carboplatin plus paclitaxel in locally advanced nasopharyngeal carcinoma in a nonendemic population.
Authors: G. Numico, M. Airoldi, P. Gabriele, A. Gabriele, M. Garzaro, L. Raimondo, F. Pedani, F. Beatrice, G. Pecorari, C. Giordano
Journal: Journal of Clinical Oncology (2010)

5569 Background: Aim of this study was the clinical evaluation of carboplatin-paclitaxel (Taxol) combination in a neoadjuvant and concomitant setting with conventional radiotherapy in locoregionally advanced nasopharyngeal carcinoma (A-NPC) in a non endemic population. Methods: Thirty patients (22M, 8F, median age: 54 yrs, median ECOG PS: 0; 27 pts type 3 and 3 pts type 2 WHO histology; 14 pts stage III, 13pts stage IVa and 3 pts IVb AJCC TNM; 21 pts N2/N3 AJCC TNM) were treated with three cycles of induction chemotherapy (IC) with carboplatin (AUC6) plus paclitaxel (Taxol) (175mg/m2) on day 1 every 3 weeks, followed by weekly carboplatin (AUC1) plus paclitaxel (Taxol) (60mg/m2) and concomitant conventional radiotherapy (70Gy) (RT). Results: After IC: 33% complete responses (CRs), 60% partial responses (PRs), 6.6% no change; after CT+RT: 87% CRs, 13% PRs. After a median follow-up of 49 months (range 16-89 months): 3 and 5 yrs progression free survival was 80% and 75% respectively and overall survival was 85% and 80% respectively; 5 yrs locoregional control was 90% and 5 yrs distant metastases free survival was 85%; toxicity of IC was: neutropenia 83% (G3 33%, G4 50%), thrombocytopenia 13% (G3), anaemia 10% (G3) and mucositis 6.6% (G3); toxicity of CT+RT was: neutropenia 63% (G4 16%), thrombocytopenia 10% (G3), anaemia 17% (G3), mucositis (G3 54%, G4 16%), skin toxicity 23% (G3) and neurotoxicity 10% (G3). Conclusions: Neoadjuvant chemotherapy with such protocol represents a feasible, efficient treatment for patients with A-NPC, ensuring excellent locoregional disease control and overall survival with low incidence of distant metastases. No significant financial relationships to disclose.
Initial phase I clinical and pharmacokinetic assessment of G4544, an oral gallium-containing compound
Authors: S. C. Novick, T. N. Julian, S. Majuru, M. Mangelus, B. D. Brown, B. Mehta, R. P. Warrell
Journal: Journal of Clinical Oncology (2008)

8592 Background: An intravenous dose of gallium nitrate (54.5–81.7 mg/m2/day gallium for 5–7 days) is effective treatment for patients (pts) with cancer-related hypercalcemia. Preliminary studies showed consistent anticancer activity in pts with non-Hodgkin's lymphoma (NHL). Low gallium doses by subcutaneous (SC) injection significantly reduced metabolic markers of disordered bone turnover in Paget's disease. A multi-year multiple myeloma study showed significantly reduced bone loss in pts receiving chemotherapy and was possibly associated with increased survival when low doses of gallium were administered SC. In preclinical studies, gallium potently inhibited osteoclast-mediated bone resorption and may have anabolic effects on bone formation. Gallium-containing compounds such as gallium nitrate have low oral bioavailability. We investigated oral absorption of gallium-containing compounds and developed G4544. G4544 showed increased oral gallium absorption (2.2-fold increase in AUC and 2.8-fold increase in Cmax as measured in preclinical studies). G4544 (30 mg gallium) was rapidly absorbed in dogs and achieved a mean peak plasma level of 1,800 ng/mL, a level 4-fold higher than that achieved with gallium nitrate alone. We report initial clinical results. Methods: G4544 tablets containing 30 mg of gallium were formulated with a proprietary delivery agent (Emisphere Technologies). Thirty volunteers (6 per dose) received G4544 at single doses ranging from 30 to 150 mg. Plasma samples were assayed to evaluate pharmacokinetics. Results: The highest dose yielded a peak plasma gallium concentration of 485 ng/mL. Plasma levels increased with escalating doses. No drug-related adverse effects were observed across the dose range examined (up to 150 mg). Conclusions: Oral administration of G4544 yields plasma concentrations of gallium known to be effective in skeletal and neoplastic diseases. Follow-up trials will seek to demonstrate bioequivalence to intravenous gallium nitrate and evaluate G4544 clinical activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genta Incorporated Genta Incorporated
Update of a phase I-II study of biweekly irinotecan in combination with gemcitabine (G), 5FU (F), leucovorin (LV) and cisplatin (G-GLIP) in patients with metastatic pancreatic cancer
Authors: A. Goel, S. Malamud, M. Grossbard, P. Homel, M. Dietrich, P. Kozuch, T. Mirzoyev
Journal: Journal of Clinical Oncology (2005)

4112 Background: Development of systemic therapy to improve outcomes associated with gemcitabine for metastatic pancreatic cancer remains a research priority. The GFLIP regimen was designed to maximize sequence dependent synergy while attempting to minimize toxicity among the four drugs. Methods: The dose limiting toxicities and maximum tolerated dose of irinotecan as part of the G-FLIP regimen have been published. For phase II testing GFLIP consisted of sequential gemcitabine (500mg/m2) at a fixed rate of 10 mg/m2/minute, irinotecan (120 mg/m2), bolus 5-FU (400mg/m2) and LV (300mg) followed by a 24 hour 5-FU infusion (1500mg/m2) on day 1, followed by cisplatin (35mg/m2) on Day 2. Cycles were repeated every 14 days. Thirty one patients with metastatic pancreatic carcinoma treated on phase I/II trial are evaluable for toxicity and activity update. Results: 31 patients, 20 men and 11 women are evaluable. Median age is 63yrs (range = 41–78 years) and median KPS score is 70–80. With a median follow up of 118 days, estimated median time to progression (TTP) is 187 days (6.6 months). With a median follow up of 215 days estimated median survival is 229 days (8.1 months). 1 year overall survival for all patients is 40%. As per RECIST criteria, 11 (35%) patients had stable disease, 8 (25.8%) patients had a partial response and 10 (32.3%) patients had disease progression. Toxicity: Treatment was generally well tolerated. Grade 3–4 toxicities per patient were thrombocytopenia (3.2%), leukopenia (16.1%), neutropenia (22.5%), neutropenic fever (3.2%), fatigue (19.3%) and thrombosis (12%). Common Grade 1–2 toxicities were nausea /vomiting (71%), diarrhea (45%), constipation (22%) and fatigue (42%). Conclusions: G-FLIP is a novel and feasible outpatient regimen with acceptable toxicity in metastatic pancreatic cancer. Phase III evaluation should be considered if the encouraging survival outcomes are maintained. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Lilly Oncology, Pfizer Pfizer
Stable disease, diagnosis and dose are prognostic factors for survival after interleukin-2 immunotherapy
Authors: Nathan H Kwan, Brittany A Ockenfels, Charmi Patel, Gerald P Miletello, Paula R Brantley
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Recent studies have reported that the clinical benefit of interleukin-2 (IL-2) immunotherapy for metastatic renal cell carcinoma (mRCC) and melanoma (mM) may be underestimated by typically reported outcomes, instead suggesting that progression-free survival or “disease control
5-year survival with dose intensive L-FAC multimodality therapy of breast cancer
Authors: K. Jabboury, A. Wong, A. Deutsch, R. Behar, K. King, S. Thomas, C. Reilly, P. Curtis, O. Mangini
Journal: Journal of Clinical Oncology (2004)

739 Background: In order to enhance the activity of front-line anthracycline-based FAC (fluorouracil, doxorubicin, cyclophosphamide) chemotherapy; incremental dose intensification of A+C was implemented. F was delivered by continuous infusion (inf) along with leucovorin (L) modulation. Administration format was switched to concomitant alkylator/antimetabolite inf. Methods: From 6/1989 to 1/2003, consecutive breast cancer patients (pt), candidates for systemic chemotherapy, were treated in a pilot study with dose intensive L-FAC at a starting dose level: 72 hour (h) IV inf 400mg/m2/day (d) F modulated by IV bolus 200mg/m2/d X3 L, concomitantly with 24h IV d1 600-1000mg/m2 C, 48h IV d2 + d3 60mg/m2 A. 6 courses were given for stage (S) I and II and 8 for III. Increasing A+C dose level and/or shortening treatment intervals < 3 weeks with growth factors, provided intensification. Prior analysis (ASCO, 1996) revealed an achieved dose intensity 22.3/A, 307/C mg/m2/week. Hormone receptor positive patients received Tamoxifen (T) 20mg/d X5 years (Y) after completion of chemotherapy. 109 pt, ages 25–81 (median 51), were enrolled: 20 SI, 35 SIIA, 19 SIIB, 8 SIIIA, 16 SIIIB, and 11 SIV. 50 (46%) were hormone receptor negative. Results: 29 (30%) non-metastatic pt underwent upfront mastectomy at pt/surgeon discretion. Breast conservation was addressed and successful in all upfront lumpectomy (45) pt., and neoadjuvant L-FAC in 6/6 SII and 15/18 SIII. 72 pt received radiation (64 after breast conservation, 8 to chest wall). Two intramammary failures were seen (3%). The median follow up is 56 months (M). The estimated 5Y disease free survival: 81% SI, 76% SII, 78% SIII. 4/11 SIV were treated, as IV NED and 3 remain relapse free at 3, 8, and 9Y. 5Y survival is 89%SI, 89%SII, and 83% SIII. By 1998, 3 pt developed AML/MDS (at 15, 26, and 36M from initiation of L-FAC) and accordingly, subsequent treatment was given in a dose dense manner only, without additional cases observed. 11/98 (11%) had a 2nd breast cancer develop; 2 while on T. Conclusions: L-FAC is highly effective in the treatment of breast cancer and allows a high rate of breast conservation. The addition of taxane therapy is currently being evaluated. No significant financial relationships to disclose.