bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival
Authors: Howard Orion M. , Gribben John G. , Neuberg Donna S. , Grossbard Michael , Poor Christina , Janicek Milos J. , Shipp Margaret A. 
Published: February 2017

PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL). PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS). RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51). CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.
Combined-Modality Treatment for Resectable Metastatic Colorectal Carcinoma to the Liver: Surgical Resection of Hepatic Metastases in Combination With Continuous Infusion of Chemotherapy—An Intergroup Study
Authors: Kemeny M. Margaret , Adak Sudeshna , Gray Bruce , Macdonald John S. , Smith Thomas , Lipsitz Stuart , Sigurdson Elin R. , O’Dwyer Peter J. , Benson Al B. 
Published: February 2017

PURPOSE: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated. PATIENTS AND METHODS: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival. RESULTS: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P = .04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P = .03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P = .60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P = .19) CONCLUSION: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.
Volume of Lymphatic Metastases Does Not Independently Influence Prognosis in Colorectal Cancer
Authors: Wong Jan H. , Steinemann Susan , Tom Paul , Morita Shane , Tauchi-Nishi Pamela 
Published: February 2017

PURPOSE: To evaluate the prognostic relevance of the volume of nodal metastatic disease in colorectal cancer patients. PATIENTS AND METHODS: One hundred node-positive patients with T2 or T3 carcinoma of the colon or rectum after routine histologic examination of the regional nodes were studied. The metastatic tumor was measured with an ocular micrometer, and the tumor volume was determined. RESULTS: The mean lymph node metastatic tumor volume was 5.1 ± 4.99 mm3 (range, 0.05 to 83,434 mm3). There was only a weak positive correlation with number of nodes involved with metastatic disease and tumor volume in nodes (r = .45). Median follow-up was 39 months (range, 1 to 87 months). The number of nodes was highly predictive of outcome. Individuals with one to three positive nodes had a substantially better survival than individuals with four or more positive nodes (P < .001). The volume of nodal metastatic disease correlated with outcome (P = .019). Patients dying as a result of disease had substantially greater mean metastatic nodal volume than those who were alive (3,705 v 1,783 mm3; P = .036). However, the total metastatic nodal volume did not, independent of positive nodes or number of positive nodes, predict outcome. Individuals with micrometastatic nodal volume did not have improved survival when compared with individuals with macrometastatic nodal volume (P = .79). CONCLUSION: The number of nodes involved with metastatic tumor, rather the volume of metastatic involvement of the regional lymph nodes, predicts outcome. These results suggest that micrometastatic disease may have a similar prognosis as macrometastatic disease when the same number of lymph nodes are involved with metastatic tumor.
Gemcitabine Combined With Oxaliplatin in Advanced Pancreatic Adenocarcinoma: Final Results of a GERCOR Multicenter Phase II Study
Authors: Louvet C. , André T. , Lledo G. , Hammel P. , Bleiberg H. , Bouleuc C. , Gamelin E. , Flesch M. , Cvitkovic E. , de Gramont A. 
Published: February 2017

PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m2 as a 10-mg/m2/min infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy. RESULTS: Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths. CONCLUSION: Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.
Randomized, Open-Label, Phase III Study of a 28-Day Oral Regimen of Eniluracil Plus Fluorouracil Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Therapy in Patients With Metastatic/Advanced Colorectal Cancer
Authors: Schilsky Richard L. , Levin Jeremey , West William H. , Wong Alfred , Colwell Bruce , Thirlwell Michael P. , Ansari Rafat H. , Bell William N. , White Robin L. , Yates Barbara B. , McGuirt Paul V. , Pazdur Richard 
Published: February 2017

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m2/1.15 mg/m2 twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m2/20 mg/m2 once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P = .01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P = .354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.
Simplified Staging for Hepatocellular Carcinoma
Authors: Vauthey Jean-Nicolas , Lauwers Gregory Y. , Esnaola Nestor F. , Do Kim-Anh , Belghiti Jacques , Mirza Nadeem , Curley Steven A. , Ellis Lee M. , Regimbeau Jean-Marc , Rashid Asif , Cleary Karen R. , Nagorney David M. 
Published: February 2017

PURPOSE: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. PATIENTS AND METHODS: The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. RESULTS: Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P = .6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P = .5). Independent predictors of death were major vascular invasion (P < .001), microvascular invasion (P = .001), severe fibrosis/cirrhosis of the host liver (P = .001), multiple tumors (P = .007), and tumor size greater than 5 cm (P = .01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P < .001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P = .3). CONCLUSION: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.
Cancer Incidence in a Population of Jewish Women at Risk of Ovarian Cancer
Authors: Liede Alexander , Karlan Beth Y. , Baldwin Rae Lynn , Platt Lawrence D. , Kuperstein Graciela , Narod Steven A. 
Published: February 2017

PURPOSE: To evaluate the incidence and clinical characteristics of ovarian and other cancers in a cohort of women at risk of developing ovarian cancer. PATIENTS AND METHODS: The Gilda Radner Ovarian Cancer Detection Program in Los Angeles, CA, was established in 1991 to study the efficacy of screening in the early detection of ovarian cancer. We present findings from a historical cohort of 290 Jewish women who were offered BRCA testing for three common founder mutations (BRCA1 185delAG and 5382insC and BRCA2 6174delT). RESULTS: In 10 years, 17 cancers were observed (1,111 per 100,000 per year), including six breast and eight ovarian or related cancers. A high proportion of cancers of peritoneal origin was observed. The majority (86%) of women with incident breast or ovarian/peritoneal cancer carried a mutation in the BRCA1 gene. The overall cancer incidence among carriers of mutations in the BRCA1 gene was estimated to be 5,450 per 100,000 per year, corresponding to a cumulative incidence of 47.5% at 10 years. In contrast, the cumulative incidence of cancer among noncarriers was 2.5% (P < 10−8). After adjustment for sampling, the risks to BRCA1 mutation carriers at 10 years were estimated to be 21% for ovarian/peritoneal/tubal cancer, 16% for breast cancer, and 36% for all cancers. CONCLUSION: The excess risk of breast and ovarian cancer in Jewish women with a family history of ovarian cancer is largely attributable to mutations in BRCA1. Intensive surveillance by use of CA-125 and ultrasound does not seem to be an effective means of diagnosing early-stage ovarian cancer in this high-risk cohort.
Phase II Trial of Docetaxel and Cisplatin Combination Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
Authors: Glisson Bonnie S. , Murphy Barbara A. , Frenette Gary , Khuri Fadlo R. , Forastiere Arlene A. 
Published: February 2017

PURPOSE: To assess the antitumor activity and toxicity of docetaxel plus cisplatin chemotherapy in patients with recurrent or incurable squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with recurrent or incurable SCCHN were eligible if they were chemotherapy naive or if they had received one prior regimen as neoadjuvant or concurrent treatment with radiation. Patients who had received chemotherapy for recurrence or prior taxanes were ineligible. Patients received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1; cycles were repeated every 21 days. RESULTS: Toxic effects and length of survival were assessable in 36 patients and tumor response was assessable in 32, for whom the overall response rate was 40% (13 of 32) (6% complete response and 34% partial response). Median time to response was 5 weeks, and median duration was 4.9 months. In the intent to treat population (n = 36), median time to disease progression was 4 months. Median survival (n = 36) was 9.6 months, and the 12-month survival rate was 27%. Grade 4 neutropenia was observed in 71% of patients. Two patients (6%) experienced serious fever during grade 4 neutropenia (without documented infection) that required intravenous antibiotics, and an additional four patients had grade 3 infection. Other severe (grades 3 and 4) toxic effects were asthenia (25%), nausea (11%), fever (8%), vomiting (8%), severe hypersensitivity reactions (8%), and diarrhea (8%). Severe stomatitis (grade 3) occurred in only one patient. CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable safety profile for palliation of recurrent SCCHN. Relative to the standard regimen of cisplatin/fluorouracil, this regimen may offer higher tumor response and survival rates with short outpatient administration and a lower incidence of severe mucosal toxicity.
Cisplatin, Dacarbazine With or Without Subcutaneous Interleukin-2, and Interferon Alfa-2b in Advanced Melanoma Outpatients: Results From an Italian Multicenter Phase III Randomized Clinical Trial
Authors: Ridolfi Ruggero , Chiarion-Sileni Vanna , Guida Michele , Romanini Antonella , Labianca Roberto , Freschi Andrea , Lo Re Giovanni , Nortilli Rolando , Brugnara Sonia , Vitali Patrizia , Nanni Oriana 
Published: February 2017

PURPOSE: Phase II and III studies have shown that the addition of interleukin-2 (IL-2) and interferon alfa-2b (IFNα-2b) in multiagent chemotherapy (CT) for advanced melanoma increases overall response (OR), albeit without clear evidence of an improvement in overall survival (OS). Treatment with high-dose IL-2 can cause severe toxicity and is normally administered in an inpatient setting. We conducted a multicenter prospective randomized clinical trial in outpatients with metastatic melanoma to compare CT with biochemotherapy (bioCT) using immunomodulant doses of IL-2 and IFNα-2b. PATIENTS AND METHODS: One hundred seventy-six eligible patients with advanced melanoma were randomized to receive CT (cisplatin and dacarbazine with or without carmustine every 21 days) or bioCT comprising the same CT regimen followed by low-dose subcutaneous IL-2 for 8 days and IFNα2b three times a week, both for six cycles. RESULTS: At a median follow-up of 18 (CT) and 16 (bioCT) months, median OS was 9.5 versus 11.0 months (P = .51), respectively. In the 89 CT-arm patients, 18 ORs (20.2%) (three complete responders [CRs] and 15 partial responders [PRs]) were observed according to World Health Organization criteria. In the 87 bioCT-arm patients, 22 ORs (25.3%) (three CRs and 19 PRs) (P = .70) were recorded. Treatment-related toxicity was fairly similar in both arms. CONCLUSION: The addition of low-dose immunotherapy did not produce a statistically significant advantage in OS, time to progression, or OR. However, the 11-month median OS in the bioCT arm does not differ greatly from the best results with high-dose IL-2–containing regimens reported in the literature. Furthermore, our treatment schedule was carried out on outpatients and had an acceptable level of toxicity.
Survival and Failure Patterns of High-Grade Gliomas After Three-Dimensional Conformal Radiotherapy
Authors: Chan June L. , Lee Susan W. , Fraass Benedick A. , Normolle Daniel P. , Greenberg Harry S. , Junck Larry R. , Gebarski Stephen S. , Sandler Howard M. 
Published: February 2017

PURPOSE: The goal of three-dimensional (3-D) conformal radiation is to increase the dose delivered to tumor while minimizing dose to surrounding normal brain. Previously it has been shown that even escalated doses of 70 to 80 Gy have failure patterns that are predominantly local. This article describes the failure patterns and survival seen with high-grade gliomas given 90 Gy using a 3-D conformal intensity-modulated radiation technique. PATIENTS AND METHODS: From April 1996 to April 1999, 34 patients with supratentorial high-grade gliomas were treated to 90 Gy. For those that recurred, failure patterns were defined in terms of percentage of recurrent tumor located within the high-dose region. Recurrences with more than 95% of their volume within the high-dose region were considered central; those with 80% to 95%, 20% to 80%, and less than 20% were considered in-field, marginal, and distant, respectively. RESULTS: The median age was 55 years, and median follow-up was 11.7 months. At time of analysis, 23 (67.6%) of 34 patients had developed radiographic evidence of recurrence. The patterns of failure were 18 (78%) of 23 central, three (13%) of 23 in-field, two (9%) of 23 marginal, and zero (0%) of 23 distant. The median survival was 11.7 months, with 1-year survival of 47.1% and 2-year survival of 12.9%. No significant treatment toxicities were observed. CONCLUSION: Despite dose escalation to 90 Gy, the predominant failure pattern in high-grade gliomas remains local. This suggests that close margins used in highly conformal treatments do not increase the risk of marginal or distant recurrences. Our results indicate that intensification of local radiotherapy with dose escalation is feasible and deserves further evaluation for high-grade gliomas.
Gemcitabine, Carboplatin, and Paclitaxel for Patients With Carcinoma of Unknown Primary Site: A Minnie Pearl Cancer Research Network Study
Authors: Greco F. Anthony , Burris Howard A. , Litchy Sharlene , Barton John H. , Bradof James E. , Richards Paul , Scullin Daniel C. , Erland Joan B. , Morrissey Lisa H. , Hainsworth John D. 
Published: February 2017

PURPOSE: To evaluate the efficacy and toxicity of the novel chemotherapy combination that includes gemcitabine, carboplatin, and paclitaxel in the treatment of patients with carcinoma of unknown primary site. PATIENTS AND METHODS: One hundred twenty patients were treated with the following regimen, administered every 21 days for a planned four courses: gemcitabine 1,000 mg/m2 intravenously (IV) on days 1 and 8, carboplatin at an estimated area under the concentration-time curve of 5 mg min/mL IV on day 1, and paclitaxel 200 mg/m2 IV on day 1. After four courses, stable and responding patients were given weekly paclitaxel 70 mg/m2 IV for 6 weeks for three 8-week courses. All patients had relatively poor prognostic features. Sixty-three patients had well-differentiated adenocarcinoma, 56 patients had poorly differentiated carcinoma, and 104 patients had performance status of 0 or 1. RESULTS: Twenty-eight (25%) of 113 assessable patients (95% confidence interval, 22% to 30%) had major objective responses to treatment. Response rates were similar in the two major histologic types. Response rate did not seem to be improved by continued therapy with weekly paclitaxel. The median progression-free survival time was 6 months. Median survival for the entire group was 9 months, and the actuarial survival at 1 and 2 years was 42% and 23%, respectively. CONCLUSION: Combination chemotherapy with gemcitabine, carboplatin, and paclitaxel followed by weekly paclitaxel is an active and tolerable treatment for patients with carcinoma of unknown primary site. The survival seen in this poor-prognosis group of patients in this multicenter community-based trial is notable and similar to other taxane-based regimens for these patients. Study of additional combinations or sequences of newer drugs, as well as the exploration of targeted biologic agents for patients with an identified target in their tumors, is warranted.