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Clinical Colorectal Cancer
  • Clinical Colorectal Cancer Volume 10 Issue 3 Frontend

    Clinical Colorectal Cancer Volume 10 Issue 3 Frontend

    • Content Type Journal Article
    • Category Cover, Masthead & Table of Contents
    • Pages 1-4
    • Authors
      • CIG Media Group


  • A Phase II Study of Oxaliplatin, Dose-intense Capecitabine, and High-dose Bevacizumab in the Treatment of Metastatic Colorectal Cancer

    Background: This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer. Patients and Methods: Nineteen patients with previously untreated advanced colorectal cancer received capecitabine at 1000 mg/m2 twice a day on days 1-5 and days 8-12 of a 14-day cycle, and OHP at 85 mg/m2 and bevacizumab at 10 mg/kg every 2 weeks. Because of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m2. Thirty-one additional patients were treated at the lower capecitabine dose. Treatment continued until disease progression, persistent intolerable toxicity, or physician and/or patient discretion. Results: Overall, toxicities were better managed and tolerated at the 850 mg/-m2 capecitabine dose. The most common treatment-related grade ≥ 3 toxicities were diarrhea and sensory neuropathy. In the first 19 subjects, the response rate was 63% (95% confidence interval [CI], 38%-84%) and 5 patients had stable disease; median progression-free survival (PFS) was 10.1 months (95% CI, 5.7-19.5 months). In the subsequent 31 patients, the response was 42% (95% CI, 25%-61%); 11 patients had stable disease and median PFS was 10.4 months (95% CI, 6.9-15.4); median overall survival was 24.8 months (95% CI, 12.9-39.7). Conclusions: This novel regimen of capecitabine at 850 mg/m2 twice a day on days 1-5 and days 8-12 and OHP at 85 mg/m2and bevacizumab at 10 mg/kg every 14 days is clinically active in advanced colorectal cancer. The toxicity profile of this regimen is consistent with the standard every-3-week dosing schedule.

    • Content Type Journal Article
    • Category Current Trial
    • Pages 210-216
    • DOI 10.1016/j.clcc.2011.03.018
    • Authors
      • Nan Soon Wong, Duke University Medical Center, Durham, NC
      • Nishan H. Fernando, Duke University Medical Center, Durham, NC
      • Johanna C. Bendell, Duke University Medical Center, Durham, NC
      • Michael A. Morse, Duke University Medical Center, Durham, NC
      • Gerard C. Blobe, Duke University Medical Center, Durham, NC
      • Wanda Honeycutt, Duke University Medical Center, Durham, NC
      • Herbert Pang, Duke University Medical Center, Durham, NC
      • Herbert I. Hurwitz, Duke University Medical Center, Durham, NC


  • Revised TNM Staging for Colorectal Cancer: Did We Miss the Golden Opportunity to Do Right By the Staging?

    Revised TNM Staging for Colorectal Cancer: Did We Miss the Golden Opportunity to Do Right By the Staging?

    • Content Type Journal Article
    • Category Letter to the Editor
    • Pages 207-209
    • DOI 10.1016/j.clcc.2011.03.016
    • Authors
      • Jay Nayak, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
      • Sanjay Goel, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY


  • Body Surface Area–based Dosing of 5-Fluoruracil Results in Extensive Interindividual Variability in 5-Fluorouracil Exposure in Colorectal Cancer Patients on FOLFOX Regimens

    Body Surface Area–based Dosing of 5-Fluoruracil Results in Extensive Interindividual Variability in 5-Fluorouracil Exposure in Colorectal Cancer Patients on FOLFOX Regimens

    • Content Type Journal Article
    • Category Commentary
    • Pages 203-206
    • DOI 10.1016/j.clcc.2011.03.015
    • Authors
      • Jennifer Saam, Myriad Genetic Laboratories, Inc, Salt Lake City, UT
      • Gregory C. Critchfield, Myriad Genetic Laboratories, Inc, Salt Lake City, UT
      • Stephanie A. Hamilton, Myriad Genetic Laboratories, Inc, Salt Lake City, UT
      • Benjamin B. Roa, Myriad Genetic Laboratories, Inc, Salt Lake City, UT
      • Richard J. Wenstrup, Myriad Genetic Laboratories, Inc, Salt Lake City, UT
      • Rajesh R. Kaldate, Myriad Genetic Laboratories, Inc, Salt Lake City, UT


  • Fatal Diffuse Alveolar Damage Associated with Oxaliplatin Administration

    Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer in both the adjuvant and metastatic disease settings. Significant improvements in survival have resulted from the use of oxaliplatin-based combinations. This article describes the use of oxaliplatin-based chemotherapy in a patient with stage III colon cancer who developed fatal diffuse alveolar damage during his adjuvant therapy. Other cases of pulmonary toxicity associated with oxaliplatin use are presented and the proposed pathophysiology of this rare occurrence is discussed.

    • Content Type Journal Article
    • Category Case Report
    • Pages 198-202
    • DOI 10.1016/j.clcc.2011.03.019
    • Authors
      • Jack Watkins, Division of Pharmacy
      • Julian H. Slade, Division of Pharmacy
      • Alex Phan, Department of Gastrointestinal Medical Oncology
      • Cathy Eng, Department of Gastrointestinal Medical Oncology
      • Annikka Weissferdt, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
      • Michael J. Overman, Department of Gastrointestinal Medical Oncology


  • Lactic Acidosis and Colon Cancer: Oncologic Emergency?

    We report the case of a 44-year-old woman who presented shortly after the diagnosis of metastatic colon cancer with profound lactic acidosis in the absence of tissue hypoperfusion or hypoxemia. Her acid-base disturbance was unresponsive to medical management but resolved after initiation of systemic chemotherapy. In addition to malignancy associated lactic acidosis, this case illustrates several other issues, including factors involved in choosing the initial chemotherapy regimen and sequencing subsequent therapies, and the role of carcinoembryonic antigen (CEA) in following response to treatment. It is important to report this case of a rare but serious complication of malignancy in order to increase recognition and understanding of this presentation.

    • Content Type Journal Article
    • Category Case Report
    • Pages 194-197
    • DOI 10.1016/j.clcc.2011.03.020
    • Authors
      • Anne M. Espinoza, University of California, San Francisco
      • Alan P. Venook, University of California, San Francisco


  • Expression of the Antiapoptotic Protein Survivin in Colon Cancer

    Background: The antiapoptotic protein survivin has been demonstrated to play an important role in colorectal carcinogenesis. However it is unclear whether the upregulation of survivin is maintained through progressive stages of disease, or if other apoptosis-related genes are coexpressed and/or repressed. We sought to evaluate survivin expression in colonic neoplasia and identify relationships with additional regulators of apoptosis. Patients and Methods: Tissue samples from 168 patients with primary colorectal cancer were profiled using the GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) and evaluated for survivin expression. Immunohistochemical staining for survivin and a panel of apoptosis-associated proteins were used in 86 patients with tissue microarray (TMA) blocks; scoring was by stain intensity and percentage of positive cells (range, 0-9). Results:Survivin mRNA was upregulated (1.8-fold increase) in primary colon cancers— irrespective of American Joint Committee on Cancer (AJCC) stage— and metastases compared with normal colonic tissue (P < .0001). Survivin staining was positive in 93% of adenocarcinomas (median immunohistochemistry [IHC] score: 2 [range, 1-6]), 100% of adenomas (1 [range,1- 2]), and 43% of normal colonic mucosa (1, [range 1-2]) (P = .006). Survivin expression increased with worsening tumor grade (P < .05). In colon cancers, survivin expression positively correlated with the coexpression of PUMA (P < .001), TACE (P = .003), and MCL1 (P = .01), and trended toward an inverse correlation with BAX (P = .058). Conclusions:Survivin expression increases during the normal mucosa-adenoma-carcinoma sequence and is maintained throughout progression of disease, which strengthens its appeal as a therapeutic target. Furthermore, we have demonstrated co-overexpression of several other apoptosis-related genes, which may in turn serve as additional and potentially synergistic therapeutic targets.

    • Content Type Journal Article
    • Category Original Study
    • Pages 188-193
    • DOI 10.1016/j.clcc.2011.03.014
    • Authors
      • Jonathan M. Hernandez, Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL
      • Jeffrey M. Farma, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
      • Domenico Coppola, Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL
      • Ardeshir Hakam, Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL
      • William J. Fulp, Department of Bioinformatics, Moffitt Cancer Center, Tampa, FL
      • Dung-Tsa Chen, Department of Bioinformatics, Moffitt Cancer Center, Tampa, FL
      • Erin M. Siegel, Department of Cancer Risk, Detection and Surveillance Moffitt Cancer Center, Tampa, FL
      • Timothy J. Yeatman, Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL
      • David Shibata, Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL


  • Laparoscopic Radical Correction Combined With Extensive Lymphadenectomy and Pelvic Autonomic Nerve Preservation for Mid-to-Low Rectal Cancer

    Objective: The purposes of this study were to confirm the definite metastasis and micrometastasis rate of upward and lateral lymph nodes of mid-to-low rectal cancer at stage II and stage III, and to evaluate the feasibility and safety of laparoscopic radical correction combined with extensive lymphadenectomy and pelvic autonomic nerve preservation (PANP). Methods: The study was performed in 68 patients who were diagnosed with mid-to-low rectal cancer at stage II or stage III and received laparoscopic radical correction combined with extensive lymphadenectomy and PANP from June 2006 to June 2008 in the General Surgery Department of Southwest Hospital. All lymph nodes resected in the surgeries were examined by hematoxylin and eosin (H & E) stain and immunohistochemistry with an antibody against cytokeratin 20 (CK20) to confirm the conditions of metastasis and micrometastasis. We compared the postoperative complications with those of traditional surgeries. Results: In 1571 lymph nodes, 16 lymph nodes were found to have definite metastasis in 6 patients (8.8%) and in 41 lymph nodes we found micrometastasis in 12 patients (17.6%). The total metastasis rate of upward and lateral lymph nodes was 19.1%. Compared with traditional surgeries, the new surgery had less blood loss and short convalescence and postoperative complications were not increased. Conclusion: The total metastasis rate of upward and lateral lymph nodes is 19.1%. The laparoscopic radical correction combined with extensive lymphadenectomy and PANP is feasible and safe.

    • Content Type Journal Article
    • Category Original Study
    • Pages 183-187
    • DOI 10.1016/j.clcc.2011.03.025
    • Authors
      • Tao Liu, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Chao Zhang, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • PeiWu Yu, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Jun Chen, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Dongzhu Zeng, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Lu Gan, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Wei Lv, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • LiYe Liu, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China
      • Xiaochu Yan, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chong Qing, China


  • Durable Complete Responses in Metastatic Colorectal Cancer Treated with Chemotherapy Alone

    Background/Purpose: The median survival for patients with metastatic colorectal cancer (mCRC) has progressively increased over the past decades. Since the introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic resection of metastases, and more recently the adoption of newer chemotherapeutic regimens associated with targeted therapy, the gains are getting more substantial. Despite the recognition of the potential for long-term survival after surgical resection of metastatic disease, long-term survival data to determine the potential curative role of chemotherapy alone is lacking. Methods: We performed a retrospective review of 2751 patients who presented with mCRC at The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years who achieved complete response with chemotherapy and were not submitted to any surgical or interventional procedures directed to the metastatic sites were included in the analysis. Results: The 5-year overall survival rate for all patients with mCRC during this period was 10.8%. Among these long-term survivors, 2.2% achieved a sustained complete response after chemotherapy (all 6 with fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were without evidence of disease until the last follow-up visit (median of 10.3 years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC included in this review. Conclusion: Cure with chemotherapy alone is possible for a very small number of patients with metastatic colorectal cancer. Improved therapies are increasing complete response rates, but the impact of modern chemotherapy on durable complete responses will require additional follow up.

    • Content Type Journal Article
    • Category Original Study
    • Pages 178-182
    • DOI 10.1016/j.clcc.2011.03.023
    • Authors
      • Renata Ferrarotto, Hospital Sírio Libanês, São Paulo, Brazil
      • Priyanka Pathak, University of Texas MD Anderson Cancer Center, Houston, TX
      • Dipen Maru, University of Texas MD Anderson Cancer Center, Houston, TX
      • Atin Agarwal, University of Texas MD Anderson Cancer Center, Houston, TX
      • Michael Overman, University of Texas MD Anderson Cancer Center, Houston, TX
      • Paulo M. Hoff, Hospital Sírio Libanês, São Paulo, Brazil
      • Scott Kopetz, University of Texas MD Anderson Cancer Center, Houston, TX


  • An Open-label, Single-arm, Phase 2 Trial of Panitumumab Plus FOLFIRI as Second-line Therapy in Patients with Metastatic Colorectal Cancer

    Background: This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line panitumumab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI). Methods: This phase 2, open-label, single-arm study enrolled patients with unresectable, measurable metastatic colorectal cancer (mCRC) after failure of first-line treatment with oxaliplatin-based chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI every 2 weeks until disease progression or intolerability. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS status was determined by real-time polymerase chain reaction (PCR) on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status. Results: Of 116 patients enrolled, 109 patients with known tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant KRAS had a complete or partial response to treatment. Median PFS was 26 weeks (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76 weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea (74%) were the most common AEs. Conclusion: Panitumumab plus FOLFIRI numerically improved objective response rate, PFS, and OS in favor of patients with wild-type KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI trials in similar patient populations.

    • Content Type Journal Article
    • Category Original Study
    • Pages 171-177
    • DOI 10.1016/j.clcc.2011.03.022
    • Authors
      • Allen L. Cohn, Rocky Mountain Cancer Center, Denver, CO
      • Grace C. Shumaker, Jackson Oncology Associates, Jackson, MS
      • Pankaj Khandelwal, West Texas Cancer Center, Odessa, TX
      • David A. Smith, Northwest Cancer Specialists, PC, Vancouver, WA
      • Marcus A. Neubauer, Kansas City Cancer Center, Overland Park, KS
      • Nilesh Mehta, Oncology Hematology Associates of Northern Illinois, Ltd, Gurnee, IL
      • Donald Richards, Texas Oncology, Tyler, TX
      • David L. Watkins, USO-Allison Cancer Center, Midland, TX
      • Kathy Zhang, Amgen Inc, San Francisco, CA
      • Mohamed R. Yassine, Amgen Inc, Thousand Oaks, CA


  • A Review of Excision Repair Cross-complementation Group 1 in Colorectal Cancer

    Oxaliplatin-based chemotherapy is the standard of care in patients with high-risk stage II and stage III colorectal cancer as well as in patients with advanced disease. Unfortunately, a large proportion of patients offered oxaliplatin fail to benefit from it. In the era of personalized treatment, there are strong efforts to identify biomarkers that will predict efficacy to oxaliplatin-based treatments. Excision repair cross-complementation group 1 (ERCC1) is a key element in the nucleotide excision repair (NER) pathway, which is responsible for repairing DNA adducts induced by platinum compounds. ERCC1 has recently been shown to be closely associated with outcome in patients with non–small-cell lung cancer (NSCLC): both high ERCC1 protein and gene expression are associated with resistance to cisplatin-based chemotherapy and better outcome without treatment. Therefore, ERCC1 has the potential to be used as a strong candidate biomarker, both predictive and prognostic, for colorectal cancer. This review will focus on the preclinical and clinical evidences supporting ERCC1 as a major molecule in oxaliplatin resistance. In addition, the important technologies used to assess ERCC1 gene and protein expression will be highlighted.

    • Content Type Journal Article
    • Category Review
    • Pages 157-164
    • DOI 10.1016/j.clcc.2011.03.024
    • Authors
      • Pierre Bohanes, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA
      • Melissa J. LaBonte, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA
      • Heinz-Josef Lenz, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA


  • An Algorithm for the Management of Hypertension in the Setting of Vascular Endothelial Growth Factor Signaling Inhibition

    Vascular endothelial growth factor (VEGF) signaling is considered to be one of the key factors involved in tumor-associated angiogenesis. Inhibition of angiogenesis has significantly improved anticancer therapy making it one of the cornerstones of treatment for various solid tumors. Several antiangiogenesis inhibitory compounds (eg, bevacizumab, sunitinib, sorafenib) are now widely used in the treatment of patients with colorectal, non–small-cell lung, advanced renal cell, hepatocellular, and breast cancer. One of the most commonly observed side effects of inhibition of VEGF signaling is hypertension, which is dose-dependent and varies in incidence among the different angiogenesis inhibitor drugs. Poorly controlled hypertension not only can lead to cardiovascular events, renal disease, and stroke, but may also necessitate discontinuation of anticancer therapy, thereby potentially limiting overall clinical benefit. In contrast, hypertension induced by VEGF inhibitors has been shown to represent an important pharmacodynamic biomarker of oncologic response. For the practicing oncologist, knowledge and optimal management of this toxicity is essential. Because of the lack of controlled studies on this topic, no clear recommendations are available. In this article, we review the available preclinical and clinical data on the pathogenesis and management of hypertension resulting from anti-VEGF inhibitor therapy and propose a treatment algorithm that our group has now implemented for daily clinical practice.

    • Content Type Journal Article
    • Category Review
    • Pages 151-156
    • DOI 10.1016/j.clcc.2011.03.021
    • Authors
      • M. Sitki Copur, Saint Francis Cancer Treatment Center, Grand Island, Nebraska
      • Angela Obermiller, Saint Francis Cancer Treatment Center, Grand Island, Nebraska


  • Nonsurgical Management of Esophageal Adenocarcinoma

    Background: The benefit of induction chemotherapy (IC) before chemoradiotherapy (CRT) for inoperable esophageal adenocarcinoma has not been established. To clarify toxicities and outcomes of combined modality treatment, we performed a retrospective review. Materials and Methods: Sixty-eight consecutive patients were identified. Fifty-one patients had CRT, 17 had radiotherapy (RT). Fifty-eight received IC before RT. IC consisted of 4 cycles of platinum and fluoropyrimidines followed by CRT 54 Gy with concurrent infusional 5-fluorouracil (5-FU) or capecitabine. Response to IC was assessed at 3 months and response to CRT at 3 months. Time to progression (TTP) and overall survival (OS) are reported. Results: Fifty-four patients were men and 14 were women, with median age 72 years (range, 42-87 years). There were 29 stage II, 33 stage III, 4 stage IVa, and 2 stage IVb tumors. The response 3 months after completion of treatment was 39.6%. No grade 4 toxicity was reported, but 10/58 patients had grade 3 toxicity from IC. The median TTP and OS from RT for the entire cohort was 12 months (95% confidence interval [CI], 7-18) and 16 months (95% CI, 5-27), respectively. The 1- and 2-year survival rates from diagnosis were 73% and 47%, respectively. There was no statistically significant difference in TTP or OS in patients who responded to IC compared with those who did not (median TTP 11 vs. 12 months, respectively; P = .8; median OS 15 vs. 14 months, respectively; P = .8). Conclusion: The outcome in patients with adenocarcinoma of the esophagus after CRT is comparable to unselected surgical series. Response to IC is not always an indicator of eventual outcome.

    • Content Type Journal Article
    • Category Original Study
    • Pages 165-170
    • DOI 10.1016/j.clcc.2011.03.017
    • Authors
      • Dorothy M. Gujral, Gastrointestinal Unit
      • Maria A. Hawkins, Gastrointestinal Unit
      • Barbara Grilli Leonulli, Gastrointestinal Unit
      • Susan Ashley, Royal Marsden Hospital NHS Foundation Trust, Sutton, United Kingdom
      • Ian Chau, Gastrointestinal Unit
      • David Cunningham, Gastrointestinal Unit
      • Diana Tait, Gastrointestinal Unit


  • Clinical Lung Cancer Volume 12 Issue 2 Frontend

    Clinical Lung Cancer Volume 12 Issue 2 Frontend

    • Content Type Journal Article
    • Category Cover, Masthead & Table of Contents
    • Pages 1-5
    • Authors
      • CIG Media Group


  • Survival for Metastatic Colorectal Cancer in the Bevacizumab Era: A Population-based Analysis

    Background: As of 2006, bevacizumab was available for the treatment of metastatic colorectal cancer (mCRC) in British Columbia (BC). This study compares survival between referred patients diagnosed with mCRC in 2003/2004 (pre-bevacizumab era) and 2006 (bevacizumab era). Patients and Methods: The BC cancer agency (BCCA) is a cancer network treating approximately 60% of patients with mCRC in BC. For this study, all patients in the BCCA diagnosed with mCRC in 2003/2004 and 2006 were included. The primary objective was to compare overall survival (OS) between the 2 cohorts. Results: One thousand four hundred seventeen patients were included: 969 from 2003/2004, and 448 from 2006. Between 2003/2004 and 2006, the proportion of patients treated with systemic therapy for mCRC increased (61.1% to 67.6%; P = .02). The only significant difference in treatment between the cohorts was in the proportion of patients who received bevacizumab (5.9% to 30.6%; P < .001). Median OS significantly differed between the 2 cohorts (13.8 to 17.3 months; P < .001). Median OS for patients who received systemic therapy increased (18.6-23.6 months; P = .001). Median OS for patients who did not receive systemic therapy was unchanged (6.1-5.9 months; P = .65). Conclusion: In this population-based study, median OS for mCRC significantly increased between 2003/2004 and 2006. An increase in the proportion of patients treated with systemic therapy, and the addition of bevacizumab to chemotherapy, seem to have contributed to this improvement in survival.

    • Content Type Journal Article
    • Category Original Study
    • Pages 97-101
    • DOI 10.1016/j.clcc.2011.03.004
    • Authors
      • Daniel J. Renouf, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Howard J. Lim, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Caroline Speers, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Diego Villa, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Sharlene Gill, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Charles D. Blanke, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Susan E. O'Reilly, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada
      • Hagen Kennecke, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada


  • A Phase I Study of the Chinese Herbal Medicine PHY906 as a Modulator of Irinotecan-based Chemotherapy in Patients with Advanced Colorectal Cancer

    PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38.

    • Content Type Journal Article
    • Category Review
    • Pages 85-96
    • DOI 10.1016/j.clcc.2011.03.003
    • Authors
      • Shivaani Kummar, Department of Medicine and Pharmacology, Developmental Therapeutics Program, Yale Cancer Center, Yale University School of Medicine, VACT Cancer Center, VACT Healthcare System, New Haven, CT, West Haven, CT
      • M. Sitki Copur, Saint Francis Medical Center, Grand Island, NE
      • Michal Rose, Department of Medicine and Pharmacology, Developmental Therapeutics Program, Yale Cancer Center, Yale University School of Medicine, VACT Cancer Center, VACT Healthcare System, New Haven, CT, West Haven, CT
      • Scott Wadler, Department of Medicine, Cornell Weill Medical College, New York, NY
      • Joe Stephenson, Cancer Center of the Carolinas, Greenville, SC
      • Mark O'Rourke, Cancer Center of the Carolinas, Greenville, SC
      • Wayne Brenckman, Phytoceutica, New Haven, CT
      • Robert Tilton, Phytoceutica, New Haven, CT
      • Shwu-Huey Liu, Phytoceutica, New Haven, CT
      • Zaoli Jiang, Phytoceutica, New Haven, CT
      • Tahmun Su, Phytoceutica, New Haven, CT
      • Yung-chi Cheng, Department of Pharmacology, Developmental Therapeutics Program, Yale Cancer Center, Yale University School of Medicine, New Haven, CT
      • Edward Chu, Department of Medicine and Pharmacology, Developmental Therapeutics Program, Yale Cancer Center, Yale University School of Medicine, VACT Cancer Center, VACT Healthcare System, New Haven, CT, West Haven, CT


  • The Follow-up After Radical Surgery of Colorectal Cancer: Is it Time for a "Tailored" Strategy?

    The problem of the surveillance for colorectal cancer after radical surgery is a widely debated argument. Like for other solid tumors, the issue is divided in 2 main routes: the early diagnosis of recurrence and the early diagnosis of a second primary cancer. Genetic and molecular features have been recognized as useful tools to measure these risks, however, the instruments are still insufficient to design a personalized strategy for the patient. In an era of "tailored therapies" in oncology, even the follow-up of the surgically treated patient for colorectal cancer should enter "a tailor's shop in which several competent tailors" should be available to manage a complex problem.

    • Content Type Journal Article
    • Category Original Study
    • Pages 81-84
    • DOI 10.1016/j.clcc.2011.03.002
    • Authors
      • Margherita Nannini, Department of Hematology and Oncology Sciences "L. A. Seragnoli", S. Orsola-Malpighi Hospital, University of Bologna, Italy
      • Maria Abbondanza Pantaleo, Department of Hematology and Oncology Sciences "L. A. Seragnoli", S. Orsola-Malpighi Hospital, University of Bologna, Italy
      • Guido Biasco, Department of Hematology and Oncology Sciences "L. A. Seragnoli", S. Orsola-Malpighi Hospital, University of Bologna, Italy


  • Synchronous Epithelial and Neuroendocrine Cancers of the Pancreas: Case Series of a Rare Occurrence

    The presence of neuroendocrine cells in adenocarcinomas is not an unusual finding and is well described in gastrointestinal tract cancers, eg, colorectal cancer and gastric cancer. Genetic analysis of such tumors has suggested a common multipotent progenitor stem cell origin. The prognostic significance of neuroendocrine cells in adenocarcinoma cells is unclear. There is a scant literature on synchronous pancreas ductal adenocarcinoma and pancreas neuroendocrine tumors. We report 2 cases with a purpose of discussing management strategies, prognosis, and potential etiologies of this rare presentation.

    • Content Type Journal Article
    • Category Case Report
    • Pages 146-150
    • DOI 10.1016/j.clcc.2011.03.013
    • Authors
      • Derek G. Power, Department of Medicine, Gastrointestinal Oncology Service
      • Jinru Shia, Department of Pathology
      • Peter J. Allen, Department of Surgery, Hepatopancreatobiliary Service Memorial Sloan-Kettering Cancer Center, New York, NY
      • William R. Jarnagin, Department of Surgery, Hepatopancreatobiliary Service Memorial Sloan-Kettering Cancer Center, New York, NY
      • Eileen M. O'Reilly, Department of Medicine, Gastrointestinal Oncology Service


  • Prognostic and Predictive Markers in Stage II Colon Cancer: Is There a Role for Gene Expression Profiling?

    Conventional clinical and pathologic risk factors in stage II colon cancer provide limited prognostic information and do not predict response to adjuvant 5-fluorouracil-based chemotherapy. New prognostic and predictive biomarkers are needed to identify patients with highest recurrence risk who will receive the greatest absolute risk reduction from adjuvant chemotherapy. We review below the evidence for conventional risk factors in patients with node-negative colon cancer, followed by a discussion of promising new molecular and genetic markers in this malignancy. Gene expression profiling is an emerging tool with both prognostic and predictive potential in oncology. For patients with stage II colon cancer, the Oncotype DX Colon Cancer test is now commercially available as a prognostic marker, and the ColoPrint assay is expected to be released later this year. Current evidence for both of these assays is described below, concluding with a discussion of potential future directions for gene expression profiling in colon cancer risk stratification and treatment decision making.

    • Content Type Journal Article
    • Category Review
    • Pages 73-80
    • DOI 10.1016/j.clcc.2011.03.001
    • Authors
      • Robin K. Kelley, University of California, The Helen Diller Family Comprehensive Cancer Center, San Francisco
      • Alan P. Venook, University of California, The Helen Diller Family Comprehensive Cancer Center, San Francisco


  • Mitomycin—C-Induced Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome: Cumulative Toxicity of an Old Drug in a New Era

    Mitomycin-C (MMC) is a first-line therapy for anal squamous cell carcinoma (ASCC), and it continues to be used for several other indications. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are serious complications of MMC therapy. Herein, we describe a 73-year-old woman with recurrent ASCC treated with MMC who developed chronic microangiopathic hemolytic anemia (MAHA) and thrombocytopenia after receiving a cumulative dose of 50 mg/m2. These hematologic adverse events persisted for 9 months and resolved after discontinuation of chemotherapy followed by multiple courses of oral corticosteroids. This report describes an atypically chronic and mild form of secondary TTP/HUS and discusses the possible role of corticosteroids in its management.

    • Content Type Journal Article
    • Category Case Report
    • Pages 142-145
    • DOI 10.1016/j.clcc.2011.03.012
    • Authors
      • Roland El-Ghazal, Hospital of St Raphael, New Haven, CT
      • Nikolai Podoltsev, Yale Cancer Center, Yale University School of Medicine, New Haven, CT
      • Peter Marks, Yale Cancer Center, Yale University School of Medicine, New Haven, CT
      • Edward Chu, Yale Cancer Center, Yale University School of Medicine, New Haven, CT
      • Muhammad Wasif Saif, Department of Hematology/Oncology, Columbia University College of Physicians and Surgeons, New York, NY
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