tbuckley/cabot-search huggingface dataset:
Prostate cancer incidence in 340 hypogonadal men treated with testosterone undecanoate injections (TU) for up to 7 years: Observational data from a registry study.
Authors: Ahmad Haider
Journal: Journal of Clinical Oncology (2015)

17 Background: Concerns regarding the safety of testosterone treatment, particularly regarding prostate cancer (PCa) in middle-aged and elderly men, still hamper the use of testosterone in hypogonadal men. In this study, we investigated prostate parameters incl. incidence of PCa in hypogonadal patients on long-term treatment with TU. Methods: In a prospective, cumulative registry study, 340 men (age: 57.37 ± 7.03 years) with testosterone ≤12.1 nmol/L received TU 1,000 mg every 12 weeks following an initial interval of 6 weeks for up to 7 years. Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation and then regularly every 3-6 months. In case of suspected PCa, biopsies were performed. Results: PV increased from 28.96 ± 10.41 to 29.88 ± 13.85 ml by model-adjusted 2.59 ± 0.2 ml (p&lt;0.0001). This increase was statistically significant compared to the previous year for the first four years. PSA increased from 1.74 ± 0.94 to 1.96 ± 1.03 ng/ml by model-adjusted 0.23 ± 0.52 ng/ml (p&lt;0.0001). 53 biopsies were performed in testosterone-treated patients. Of these, 5 (9.4%) were positive and 48 (90.6%) negative. The proportion of PCa in testosterone-treated patients in our registry study was 1.5% with an incidence of 30.7 per 10,000 patient years. In hypogonadal patients without testosterone treatment, 314 biopsies were performed. Of these, 111 (35.4%) were positive and 203 (64.6%) negative. In eugonadal patients, 584 biopsies were performed. Of these, 263 (40.4%) were positive and 321 (55%) negative. In total, 951 prostate biopsies were performed in our practice from 2004 through 2013, of which 379 (39.9%) were positive and 572 (60.1%) negative. Conclusions: Long-term treatment with TU in hypogonadal men undergoing regular monitoring according to EAU guidelines does not increase the incidence of PCa.
Time to first tumor progression as outcome predictor of a second trastuzumab-based therapy beyond progression in HER2-positive metastatic breast cancer
Authors: G. Metro, A. Fabi, D. Giannarelli, D. Gemma, M. Ciccarese, G. Lanzetta, P. Papaldo, V. Lorusso, E. Magnolfi, F. Cognetti
Journal: Journal of Clinical Oncology (2008)

1071 Background: Retrospective studies suggest a potential utility for continuation of trastuzumab beyond progressive disease (PD) in HER2-positive metastatic breast cancer (MBC). However, the lack of randomized data leave this issue unanswered. We hypothesized that time to first progression (TTP1) would identify those patients who would benefit the most from a second trastuzumab-based therapy beyond PD in terms of response rate (RR2) and TTP2. Methods: The medical records of 4 Italian institutions were reviewed to select the HER2-positive MBC patients treated with ≥ 2 trastuzumab-based therapies (either trastuzumab alone or in combination with chemo- and/or endocrine therapy). Median TTP1 served as a cut-off to identify two groups of patients with different sensitivity to trastuzumab beyond PD. Results: 69 patients were evaluable. Median age was 49 (range 25–79) and half of them were untreated for MBC. Median number of trastuzumab-based therapies received was 3 (range 2–5). Overall, RRs to a first and second trastuzumab-based therapies were 50.7% (95%CI: 38.2–63.2) and 27.5% (95%CI: 17.5–39.6) respectively and the corresponding values for TTP1 and TTP2 were 8 months (range 1–39) and 6.5 months (range 1–43). TTP1 identified two groups of patients (≥ 8 months, n=36 and < 8 months, n=33) with well balanced baseline characteristics. By comparing the clinical outcome of a second trastuzumab-therapy beyond PD between patients with a TTP1 ≥ and < 8 months, no significant difference was observed for RR2 (p=0.86), whereas a significant difference in favor of patients with a TTP1 ≥ 8 months was observed for TTP2 (7.6 months vs 4.5 months respectively, p=0.01). Post-progression survival, namely the time elapsing from PD on first trastuzumab and death, significantly favored patients with a TTP1 ≥ 8 months (31.8 months vs 21.8 months respectively, p=0.01). At the multivariate analysis for TTP2 only TTP1 (≥ or < 8 months) was an independent predictor of TTP2. Conclusions: TTP1 may predict the outcome of a second trastuzumab-based therapy beyond PD in HER2-positive MBC. Thus, it represents an important tool for the clinician in order to select the best treatment option for patients progressing on a first trastuzumab-based therapy. No significant financial relationships to disclose.
Comparison of 5-fluorouracil with ftorafur in adjuvant chemotherapies with combined inductive and maintenance therapies for gastric cancer.
Authors: T Nakajima, T Takahashi, K Takagi, K Kuno, T Kajitani
Journal: Journal of Clinical Oncology (1984)

A group of 243 patients with gastric cancer was subjected to a prospective randomized trial of adjuvant chemotherapy after curative gastrectomy. One of the three arms (regimen A) is induction therapy with a three-drug combination of mitomycin C (MMC), 5-fluorouracil (5-FU), and cytosine arabinoside (ara-C) followed by intermittent oral administration of 5-FU for two years (MFC + F). In regimen B, 5-FU in regimen A is replaced by ftorafur, administered on the same schedule as regimen A (MF'C + F'). Regimen C is the control, in which patients are treated by surgery alone. Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer; five-year survival rates of the subset of stages I, II, and III were 72.1% with regimen A and 53.1% with regimen C (P less than .05). Regimen B yielded a better survival than the control, although the difference did not reach statistical significance. The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer.
Pattern of care study for treatment of ovarian cancer patients among Japanese gynecologists. A Japanese Gynecologic Oncology Group (JGOG) study
Authors: K. Fujiwara, T. Sugiyama, E. Aotani, J. Kigawa, K. Kuzuya, F. Saji, K. Ochiai, K. Noda
Journal: Journal of Clinical Oncology (2006)

15029 Background: The Japanese Society of Gynecologic Oncology started a training program for the subspecialty of board certified gynecologic oncologists in 2005. This study aimed to assess the attitude of Japanese gynecologists for the treatment of ovarian cancer in pre-gynecologic oncologist era. Methods: The JGOG distributed a survey to 217 member institutions in January 2005. The principal investigator (PI) of each institution answered 33 questionnaires regarding diagnostic, surgical and chemotherapy issues. The survey was returned from 156 institutions (71.9%). Results: Hospital settings were general (44%), academic (44%), Cancer Center (8%), or private (4%). Only two of PIs were medical oncologists and rests of them were gynecologists. As the staging procedure in early ovarian cancer, 67% institutions do systemic pelvic lymphadenectomy (LNX) but 22% do only sampling. For the paraaortic nodes, 36% do systemic LNX and 10% do sampling below renal vein, and 14% do LNX and 12% do sampling below inferior mesenteric artery. However, intraabdominal explorations such as multiple peritoneal biopsies have been done only less than 30% except for omentectomy (90%). With regard to the surgery for advanced ovarian cancer, 57% institutions do not do any intestinal resection and anastomosis during the primary surgery. Among them 7% of institutions prefer neoadjuvant chemotherapy (no debulking at all) for advanced ovarian cancer. However, 84% of the institutions do interval debulking and 57% of them are quite aggressive for the procedure. These results demonstrate the high expectation that chemotherapy may reduce the aggressiveness of surgery for advanced ovarian cancer. In terms of chemotherapy for the high-risk early and advanced ovarian cancer, taxane plus platinum is the most used regimen (93–95%). However, 45% of institutions prefer different regimen for clear cell carcinoma. CPT-11 is the most used (88.6%). Intraperitoneal chemotherapy has been performed in 28.2% of institutions. 37.2% of institutions do consolidation chemotherapy. Conclusions: This is an important base-line information to assess the pattern of care for ovarian cancer patients in the era before gynecologic oncologist subspecialty is applicable in Japan. No significant financial relationships to disclose.
Trabectedin phase II clinical trials: Pooled analysis of safety in patients with solid tumors
Authors: A. Cioffi, A. LeCesne, J. Blay, S. Delaloge, A. Yovine, R. Maki, A. Nieto, J. J. Jiao, G. D. Demetri
Journal: Journal of Clinical Oncology (2009)

e13510 Background: Trabectedin is an originally marine-derived antineoplastic agent. Its unique antitumor properties, attributed to specific binding to the small groove of DNA, have been demonstrated activity against soft-tissue sarcoma (STS), ovarian, breast and prostate cancer. Trabectedin treatment has been authorized by EMEA for STS after failure of standard treatment and shows efficacy in relapsed ovarian cancer in a phase III study. This retrospective report on safety includes single-agent trabectedin phase II studies in patients (pts) with solid tumors. Methods: A total of 1,132 pts were treated with trabectedin in 19 international trials (Feb’99 - Apr’08). Three schedules were analyzed: 24-hour infusion every 3 weeks (wk) (570 pts), 3-h every 3 wk (258 pts), and 3-h for 3 out of 4 wk (304 pts). Safety analyses included pts who received at least part of 1 infusion. MedDRA and NCI-CTC v1.0/2.0 were used to code and grade treatment-emergent adverse events (AEs). Results: Median pt age was 54 years with ECOG 0–1 (&gt;99%). Diagnosis included sarcoma (56%), ovary (26%) and breast (7%) cancer, for which 90% of pts had received chemotherapy, 37.5% radiotherapy, and 96.0% surgery. Trabectedin lasted for a median of 3 cy (9.4 wks) and 28% of pts received ≥ 6 cycles, with a median dose intensity of 0.4 (0.1–0.6) mg/m 2 /wk. The overall rate of discontinuations due to toxicity was 10.3%, similar between all three dose schedules. Most common trabectedin-related AEs (≥ 20% of pts) were nausea, fatigue and vomiting. Most common lab abnormalities were reversible myelosuppression, mainly neutropenia (37% grade3–4) though G-CSF was given to less than 10% of pts; and transient transaminase increases (grade3–4: ALT, 45%; AST, 30%). Of note, only 3.7% and 5.7% of pts had alopecia or mucositis/stomatitis, respectively. Fifteen drug-related deaths (1.3%) occurred. Conclusions: Single-agent trabectedin was reasonably well tolerated, with low rates of drug-related discontinuations and deaths. Sustained clinical benefit in the absence of relevant cumulative toxicities allows its administration to patients for prolonged periods of time. [Table: see text]
Corrected area under serum hemoglobin curve (Hb c-AUC) as a predictor of maximal hemoglobin response after erythropoietin (rHuEpo) treatment in chemotherapy induced anemia patients
Authors: E. Banu, M. Levee, F. Scotte, A. Banu, S. Oudard, J. Ayllon, C. Le Maignan, B. Bonan, A. L. Le Louet, J. M. Andrieu
Journal: Journal of Clinical Oncology (2004)

9586 Background: The concentration of serum hemoglobin (Hb) during rHuEpo treatment can be used to predict Hb response probability among patients (pts) treated by chemotherapy (CT). We were able to determine whether Hb dynamics over time correlate with rHuEpo efficacy defining a new predictive factor: Hb c-AUC. Methods: Our retrospective analysis validated the Hb c-AUC concept, defined as total Area Under serum Hb Curve (Hb AUC) per unit of time. Pts had regular Hb evaluation during rHuEpo treatment until blood cell transfusion, if applicable. The trapezoidal and Simpson's rules were used to calculate the Hb AUC. Response was defined as an Hb increase of at least 1 g/dL over the treatment. Based on their Hb c-AUC values, pts were analyzed according to maximal Hb response. Cox regression and log-rank tests were used after adjustment according to the Hb baseline level. Results: A total of 91 pts were analyzed: 46 men and 45 women, with a median age 61 years; 81 pts with solid tumors and 10 pts with hematological malignancies were treated with CT. Twenty-seven pts presented bone metastases. Median rHuEpo treatment duration and Hb c-AUC value were 76 days (8–422 days) and 10,3 g/dL (6.7–13.8 g/dL), respectively. Hb response was observed in 67% of pts. There was a significant difference in Hb response in favor of the high (> 10 g/dL) vs. low (≤ 10 g/dL) Hb c-AUC level group (73% vs. 41%, p=0.002), respectively. Predictive variables for maximal Hb response in univariate analysis were lymphocyte baseline level (p=0.04) and Hb c-AUC (p=0.0001). Only Hb c-AUC variable remained significant in multivariate analysis. Transfusional requirements were reduced by 30% in favor of high Hb c-AUC group (20% vs. 50%). Conclusions: Since only a proportion of cancer anemic pts benefit from rHuEpo, a reliable means of predicting potential responders would be useful. This analysis suggests that response to rHuEpo can be earlier predicted by Hb dynamics over time: Hb c-AUC. No significant financial relationships to disclose.
Efficacy of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in early chronic phase (CML-CP)
Authors: G. Borthakur, H. M. Kantarjian, S. M. O'Brien, D. Jones, C. Koller, C. Nicaise, G. Garcia-Manero, A. Ferrajoli, J. E. Cortes
Journal: Journal of Clinical Oncology (2008)

7013 Background: Dasatinib (BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL and SRC with significant activity in pts with CML-CP resistant or intolerant of imatinib (IM). We initiated a phase II trial to study efficacy and safety of dasatinib in pts with previously untreated CML-CP. Methods: The primary objective was to estimate the proportion of pts attaining major molecular response at 12 months (mo). Pts with previously untreated CML-CP were eligible and received dasatinib 100 mg/day, randomized to either 50 mg-twice-daily (BID) or a 100 mg-once-daily (QD). Results: Forty pts have been enrolled (21 on the QD schedule, 19 BID). Median age was 41 years (yrs) (range 18–76 yrs). The rate of complete cytogenetic response [CCyR] at 3, 6 and 12 mo compares favorably to those observed in historical controls treated with imatinib 400mg or 800 mg daily (Table 1). At 12 mo, 8/25 (32%) evaluable pts had achieved a major molecular response. There was a trend for improved molecular response with the QD schedule. Grade 3–4 non-hematologic toxicity (regardless of causality) included fatigue (5%), headache (3%), and rash (3%). Pleural effusion occurred in 5 (13%) pts (all grade 1–2). Grade 3–4 hematologic toxicity (transient) were thrombocytopenia 10%, neutropenia 5%, and anemia 3%. With median follow-up of 18 mo, 18 (46%) pts required transient treatment interruption and dose reduction. The actual median daily dose for all pts was 100mg. There is no significant difference in grade 3–4 toxicity by treatment schedule. Conclusions: Rapid CCyR occurs in most patients with previously untreated CML-CP treated with dasatinib frontline therapy with a favorable toxicity profile. Accrual to this trial continues. Months on therapy Percent with CCyR (No. evaluable) P value Dasatinib Imatinib 400 mg Imatinib 800 mg 3 mo 72 (36) 37 (49) 62 (202) 0.0003 6 mo 94 (34) 54 (48) 82 (199) <0.0001 12 mo 100 (26) 65 (48) 86 (197) 0.0001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
HER-2 gene amplification in circulating tumor cells (CTCs): Concordance with amplification status in primary breast cancers and metastatic lesions
Authors: R. Yerushalmi, M. Mishaeli, D. G. Huntsman, K. A. Gelmon
Journal: Journal of Clinical Oncology (2009)

e12006 Background: Recent studies have suggested a significant incidence (10%-30%) of discordance in HER-2 expression between metastatic lesions and the primary breast cancer (BC) which can result in inappropriate treatment recommendations. Biopsies of recurrent BC can aid in determining the expression but are often painful, costly, or cause delays in therapy. We initiated a study with the objective to determine and compare the molecular characteristics of the primary tumor, CTCs and metastases to assess whether the assessment of HER-2 gene amplification status in CTCs by FISH analysis could be used to determine treatment. Methods: After consent, patients with metastatic BC were enrolled, peripheral blood was collected (5 cc-10 cc), metastases were biopsied and HER-2 expression was determined. Blood samples were used for the CTC assay. We performed the CTC enrichment assay using a combination of anti CK and anti-EpCAM. The criteria for CTCs were: positive for cytokeratins 8, 18, 19, positive for DAPI and negative for CD45. Slides were scanned for CTCs using the Ariol system. When a CTC was identified the slide was reused for HER-2 FISH staining using the PathVysion HER-2 DNA Probe Kit. Initial attempts of FISH on CTCs took 48 hours to complete; to hasten the process, the second scan for FISH was done only on selected areas and the images for CTCs and FISH analysis were fused to obtain FISH images on a specific CTCs resulting in a 1 hour process. Results: To date 58 samples were collected, 40 of which had CTCs. At present, biopsies are being assessed and compared to the primary lesion in the initial 20 cases. Conclusions: FISH analysis of CTCs is a feasible technique and may be used to assess the specific molecular characteristics of breast cancer. Whether their HER-2 status reflects the metastatic or primary tumor is still unclear but is being determined and may have useful clinical application. No significant financial relationships to disclose.
Phase I trial of cisplatin, infusional 5-FU and irinotecan in advanced gastric cancer
Authors: A. Segura, C. Fernández-Martos, J. Aparicio, J. M. Campos, J. Vicent, I. Busquier, C. Molins, V. Guillem
Journal: Journal of Clinical Oncology (2004)

2117 Background: There is not a standard chemotherapy treatment for advanced gastric cancer. Irinotecan/Cisplatin is one of the new combinations showing promising activity in this disease. Methods: This study aim to determine maximum tolerated dose (MTD) of a three drugs combination chemotherapy in patients with locally advanced non rescetable or metastatic gastric cancer. Other advanced solid tumors not previously treated for which the proposed chemotherapy is a reasonable therapeutic option could be included. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). The recommended phase II dose is defined as the dose preceding the MTD A Phase I trial, started with: Infusional 5-FU: 14 days protacted infusion, days 1 and 22, fixed dose 200 mg/m2, weekly cisplatin: fixed dose 30 mg/m2, days 1,8,22 and 29. Weekly irinotecan days 1,8,22 and 29, 3 doses levels: 0: 55 mg/m2, 1: 60 mg/m2, 2: 65 mg/m2. Irinotecan dose escalation is allowed if 0/3 or 1/6 patients had limiting toxicity at previous dose level and at least three patients were treated for the entire treatment period in each level. DLT is defined as: G4 neutropenia and trombophenia for five days or more, fever or sepsis with neutropenia and other non-hematological grade 3–4 toxicity (excluding alopecia, anaemia and vomiting). Results: Three patients were included in first level, 2 males / 1 female (ages: 21,22,56). Two advanced gastric adenocarcinoma and one hepatocarcinoma Toxicity: diarrhea grade 2: one patient, asthenia grade 2: one patient, nausea grade 2: one patient. No MTD toxicity was found. Conclusions: In December 2003, the first level is completed without DLT. The study is ongoing and there is a patient included in second level. No significant financial relationships to disclose.
Phase I/II study of concurrent chemo-radiation in combination with erlotinib for locally advanced esophageal carcinoma
Authors: S. Wu
Journal: Journal of Clinical Oncology (2008)

15670 Background: Esophageal carcinoma is one of the most common malignant tumors in China. The optimal treatment approach for esophageal carcinoma continues to be a matter of debate. Concurrent chemoradiation is superior to radiation alone as primary therapy and has been widely recognized as a viable option for locally advanced esophageal carcinoma. The patterns of failure observed after definitive chemoradiation showed that local-regional control is poor. Currently, preclinical data suggest that there may be significant potential for epidermal receptor inhibitors to enhance the effectiveness of radiation. Our planning study is to evaluate the feasibility and efficacy of erlotinib added to concurrent chemo-radiation in locally advanced esophageal squamous cell carcinoma patients. Methods: From Jan 1st to July 1st 2007, twelve patients confirmed with esophageal squamous cell carcinoma were enrolled. One patient was stage II, 6 patients were stage III, 2 patients were stage IVa, and other 3 patients were stage IVb. Patients received 60 Gy of radiation in 30 fractions. Chemotherapy was given concurrently for two cycles. Paclitaxel (135mg/m2) was infused intravenously on day 1 and day 28, and cisplatin (20mg/m2) on day 1,2,3 and 28,29,30, respectively. The drug dosage was adjusted according to the acute toxicities occurred in the first cycle. Erlotinib was administrated at the beginning of chemoradiation with 150mg/day from day1 to day 42. At completion of treatment patients underwent computed tomography scan, endoscopic ultrasound and biopsy to evaluate response to chemoradiation. Results: The patients tolerated the treatment well. The most frequent grade 3/4 toxicities of the regimen were leucopenia, esophagitis and skin rash (The details showed in table 1). Eleven patients had complete response after the treatment and biopsy were negative. One patient had partial response and biopsy displayed tumor residue. With a median of 5 months follow-up, two patients had liver metastasis and one patient had local recurrence. One patient died of liver metastasis. Conclusions: The chemoradiation plus erlotinib may improve the local control. The toxicities of therapy, while manageable, were significant. No significant financial relationships to disclose.
Tumor-associated peripheral eosinophilia: two unusual cases.
Authors: S S Reddy, R H Hyland, R E Alison, J F Sturgeon, M A Hutcheon
Journal: Journal of Clinical Oncology (1984)

Peripheral eosinophilia is a rare but recognized accompaniment of malignant disease. Two unusual cases, one with a histiocytic lymphoma and the other with cervical carcinoma, are described. In the first patient, pulmonary infiltrates developed at the height of the eosinophilia and in the second, the peripheral eosinophilia heralded the onset of disseminated disease. Tumor-associated peripheral eosinophilia is reviewed, and it is concluded that peripheral eosinophilia associated with a malignant setting is a marker of extensive disease and is thus associated with a poor prognosis.