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ABSTRACT: Treatment of unresectable locally advanced pancreatic cancer (LAPC) usually includes chemotherapy and/or radiation therapy in an attempt to downstage these tumors to the extent of resectability, but outcomes remain poor. Irreversible electroporation (IRE) is an ablative modality that may be useful in this population. The aim of this study was to evaluate the safety of percutaneous IRE in patients with pancreatic adenocarcinoma.
IRE was performed in patients with pancreatic cancer whose tumors remained unresectable after, or who were intolerant of, standard therapy. The procedures were all done percutaneously under general anesthesia. Patients were then followed for adverse events, tumor response, and survival.
Fifteen IRE procedures were performed in 14 patients (one was treated twice). Three patients had metastatic disease and 11 had LAPC. All patients had received chemotherapy previously, and 11 had received radiation. The median tumor size was 3.3 cm (range, 2.5-7 cm). Immediate and 24-hour postprocedural scans demonstrated patent vasculature in the treatment zone in all patients. Two patients underwent surgery 4 and 5 months after IRE, respectively. Both had margin-negative resections, and one had a pathologic complete response; both remain disease-free after 11 and 14 months, respectively. Complications included spontaneous pneumothorax during anesthesia (n = 1) and pancreatitis (n = 1), and both patients recovered completely. There were no deaths directly related to the procedure. All three patients with metastatic disease at IRE died from progression of their disease.
Percutaneous IRE for pancreatic adenocarcinoma is feasible and safe. A prospective trial is being planned.
Journal of vascular and interventional radiology: JVIR 12/2012; 23(12):1613-21. · 1.81 Impact Factor
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ABSTRACT: Introduction: Patients with pancreatic cancer (PC) present with advanced disease that is lethal and notoriously difficult to treat. The research focused initially on combining cytotoxic therapies with gemcitabine, and over the past decade, a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth. Areas covered: The cell cycle is a tightly regulated series of events that governs cell replication and division. Deregulation of cell cycle kinases have been implicated in PC tumorigenesis. In this review, we discuss the potential and limitations of current cyclin-kinase inhibitors. We also summarize progress in evaluating other mitotic kinase inhibitors and novel cell-cycle kinase inhibitors as potential therapeutic agents in PC. Expert opinion: While the successful development and approval of cell-cycle inhibitors for PC therapy remains unresolved, pre-clinical identification of resistant mechanisms would help design better early- phase clinical trials where relevant combinations may be evaluated prior to Phase II testing. The authors believe that cell-cycle kinases are important anti-cancer targets that operate in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by providing a unique, targeted, and complimentary anti-cancer mechanism, expand the available armamentarium against PC.
Expert Opinion on Emerging Drugs 11/2012; · 3.21 Impact Factor
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Peter J Hosein,
Jessica Macintyre,
Carolina Kawamura,
Jennifer Cudris Maldonado,
Vinicius Ernani,
Arturo Loaiza-Bonilla,
Govindarajan Narayanan,
Afonso Ribeiro,
Lorraine Portelance,
Jaime R Merchan,
Joe U Levi, Caio M Rocha-Lima
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ABSTRACT: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC).
In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate.
Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22-69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %).
FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted.
BMC Cancer 05/2012; 12:199. · 3.01 Impact Factor
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ABSTRACT: OBJECTIVE:: nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients. METHODS:: In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile. RESULTS:: Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy. CONCLUSIONS:: nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.
American journal of clinical oncology 02/2012; · 2.21 Impact Factor
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Journal of gastrointestinal oncology 06/2011; 2(2):117-21.
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ABSTRACT: Little progress has been made in the treatment of pancreatic cancer (PC). This study evaluated the clinical activity of gemcitabine, oxaliplatin, and cetuximab (GOC) in patients with locally advanced or metastatic PC.
The study primary endpoint was progression-free survival (PFS). Eligible, chemotherapy-naive PC patients were treated with gemcitabine (1000 mg/m over 100 min) on day 1, oxaliplatin (100 mg/m) on day 2, every 2 weeks, and weekly cetuximab, (loading dose of 400 mg/m on cycle 1 day 1 and 250 mg/m thereafter). It was expected that GOC treatment would extend the median PFS from 5.8 to 7.54 months, a relative increase of 30%, compared with gemcitabine and oxaliplatin (historical control).
A total of 41 evaluable patients were enrolled. The overall response rate was 24%. Median PFS time was 6.9 months and median overall survival (OS) was 11.3 months. Patients with locally advanced disease had longer median PFS (12.4 vs. 4.7 mo) and OS (15.7 vs. 6.4 mo) compared with patients with metastatic disease. The most common grade 3 to 4 toxicities included neutropenia (32%), infection (with normal or grade 1 to 2 neutropenia, in 24%), neuropathy (17%), fatigue (15%), and rash (7%). Five patients (12%) discontinued study treatment without evidence of progression. Rash was not a significant prognostic factor affecting PFS or OS.
GOC is a feasible combination with an acceptable toxicity profile. However, GOC did not significantly extend PFS in the overall patient population to consider it for further development.
American journal of clinical oncology 05/2011; 35(5):446-50. · 2.21 Impact Factor
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ABSTRACT: Diarrhea is a common side effect of chemotherapy. Pseudomembranous colitis is a well known complication of antibiotic treatment that can also be observed, albeit rarely, with certain chemotherapeutic agents. We present four cases of severe colitis in patients undergoing treatment with taxane-based chemotherapy for pancreatic, lung and breast cancer. None of them had recently received antibiotics. One patient presented with a bowel perforation and three had endoscopic findings of pseudomembranous colitis. Two of these three patients had negative stool toxin assays for Clostridium difficile. In the patient presenting with perforation, an emergency left hemicolectomy was performed and the pathological findings in the colon were acute inflammation and ischemic necrosis; the other three patients were treated with oral vancomycin and/or oral or intravenous metronidazole leading to complete resolution of the symptoms. Apart from pseudomembranous colitis, we describe patients presenting with neutropenic enterocolitis as well as ischemic colitis after docetaxel use. These cases provide some insight into the spectrum and varied clinical presentations of severe colitis associated with taxane-based chemotherapy.
World journal of gastrointestinal oncology. 10/2010; 2(10):390-4.
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ABSTRACT: Surgery remains the only curative therapy for colorectal cancer (CRC); however, several studies have proved that adjuvant chemotherapy improves the curative rate. A growing body of evidence indicates that significant deviations from recommended treatment plans are frequent. Patients may experience delays in the administration of adjuvant chemotherapy that can reduce its survival benefit. To date, few studies have examined factors associated with the timing of adjuvant chemotherapy or have described the effects of delayed therapy on overall survival. In this review, we discuss the extent and predictors of delay in administration of adjuvant chemotherapy as well as the relationship between timing and outcomes in CRC.
Clinical Colorectal Cancer 07/2010; 9(3):144-9. · 1.68 Impact Factor
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ABSTRACT: Molecularly targeted agents have dramatically impacted the management of several cancers. Targeting KIT has led to a new treatment paradigm in gastrointestinal stromal tumors (GISTs). KIT is a cell surface receptor with tyrosine kinases that, upon binding of its ligand, stem cell factor, activates various signaling pathways. Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for first- and second-line treatment of metastatic and unresectable GISTs. In this article, we will review the molecular pathogenesis of GISTs followed by a discussion of imatinib and sunitinib's role in the treatment of GISTs. Finally, we will introduce novel therapeutic options for imatinib- and sunitinib-resistant GISTs.
World Journal of Gastroenterology 06/2010; 16(22):2726-34. · 2.47 Impact Factor
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ABSTRACT: Erlotinib (Tarceva) is a small-molecule, orally dosed, anti-cancer drug that inhibits the epidermal growth factor receptor. Randomized, controlled clinical studies have demonstrated that erlotinib significantly improved survival in patients with previously treated non-small-cell lung cancer and, in combination with chemotherapy, in patients with untreated pancreatic cancer. In this article, we describe the clinical evidence and value of erlotinib as a therapy for non-small-cell lung cancer and pancreatic cancer and discuss ongoing clinical studies to optimize its use in various settings and to identify appropriate patient populations.
10/2009; 34(10):554-64. · 1.07 Impact Factor
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ABSTRACT: The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU-based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.
Clinical Colorectal Cancer 12/2008; 7(6):369-75. · 1.68 Impact Factor
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Caio M Rocha-Lima
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ABSTRACT: Complete surgical resection is the only potentially curative option for pancreatic cancer. However, most patients have advanced/metastatic disease at the time of diagnosis, or will relapse after surgery. Systemic chemotherapy is only palliative. Gemcitabine-based therapy is an acceptable standard for unresectable locally advanced/metastatic pancreatic cancer, but average median survival is only 6 months. The addition of other chemotherapies (including other antimetabolites, platinum, and topoisomerase I inhibitors) or targeted therapies (farnesyl transferase inhibitors, metalloproteinase inhibitors, cetuximab and bevacizumab) to gemcitabine has failed to improve outcome. The combination of gemcitabine and erlotinib, a small-molecule tyrosine kinase inhibitor of the human epidermal growth factor receptor, was recently approved by the US/European authorities for use in advanced disease. In a phase III trial, the combination demonstrated a significant improvement in overall survival compared with gemcitabine monotherapy. Positive efficacy results have also been observed in a phase III trial, favoring the addition of capecitabine to gemcitabine compared with gemcitabine alone. This review focuses on the recent developments in systemic treatment, and discusses how novel agents might be incorporated into future treatment strategies for pancreatic cancer.
Anti-Cancer Drugs 07/2008; 19(5):435-46. · 2.41 Impact Factor
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ABSTRACT: Recent clinical trials suggest that epidermal growth factor receptor (EGFR)-targeted agents could benefit many patients with cancer.
We review the current status of several EGFR-targeted therapies in cancer patients and address the efficacy of theses drugs as monotherapy or in combination with other drugs and/or treatments.
Cetuximab is the most widely studied anti-EGFR monoclonal antibody. Other monoclonal antibody agents under investigation are panitumumab, matuzumab, MDX-447, nimutozumab, and mAb806. Extensive research has also evaluated the efficacy of EGFR tyrosine kinase inhibitors such as erlotinib, gefitinib, EKB-569, lapatinib (GW572016), PKI-166, and canertinib (CI-1033). All of these agents have been studied for the treatment of colorectal, lung, breast, pancreatic, renal, head and neck, gynecologic, and prostate cancer. Currently, cetuximab and panitumumab are FDA approved for the treatment of metastatic colorectal cancer. Additionally, cetuximab is approved for head and neck cancer. Erlotinib is FDA approved for advanced/metastatic lung cancer. Erlotinib in combination with gemcitabine is approved for advanced/metastatic pancreatic cancer treatment.
EGFR-targeted agents have already shown utility in different scenarios. Researchers are continuously investigating additional cancer types and combined treatment modalities that could also benefit from the use of EGFR-targeted agents. Careful patient selection through the identification of specific biologic markers, such as gene expression, genomic polymorphism, and posttranslational modifications of EGFR downstream effectors, most likely will contribute to the successful use of these agents.
Cancer control: journal of the Moffitt Cancer Center 08/2007; 14(3):295-304.
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ABSTRACT: This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer.
IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety.
In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar.
IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.
Journal of Clinical Oncology 09/2004; 22(18):3776-83. · 18.37 Impact Factor
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ABSTRACT: Despite the high response rates to chemotherapy, small-cell lung cancer (SCLC) is among the most lethal malignancies. Long-term survival is anecdotal for patients with extensive disease; 5-years survival is < or =5% for those with limited disease. All patients with extensive disease and most patients with limited disease will experience disease progression and become candidates for second-line therapy. Although a number of agents have demonstrated antitumor activity in relapsed SCLC, including paclitaxel, docetaxel, etoposide, cisplatin, and carboplatin, topotecan is the only single agent currently approved in the United States for the treatment of recurrent disease. Topotecan is a novel topoisomerase I inhibitor with established antitumor activity in recurrent SCLC and has a predictable, noncumulative toxicity profile. Furthermore, topotecan has been shown to provide symptom improvement in this predominantly palliative setting. Evidence also suggests that topotecan readily penetrates the blood-brain barrier and might be active in the relatively large subset of SCLC patients who experience brain metastases. This article reviews the clinical utility of topotecan in recurrent SCLC, including its efficacy, tolerability, and quality-of-life effect, when used as monotherapy and in novel combination regimens.
Lung Cancer 07/2003; 40(3):229-36. · 3.43 Impact Factor
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ABSTRACT: Small-cell lung cancer (SCLC) accounts for 20%-25% of all new cases of lung cancer and represents the sixth most commonly diagnosed cancer in the United States. Given the tumor's systemic nature and chemoresponsiveness, chemotherapy has become the cornerstone of its management. Chemotherapy significantly prolongs survival; however, most of the patients still die within 2 years of diagnosis. Combination chemotherapy represents the treatment of choice for this disease. In the United States, cisplatin/etoposide is the regimen most frequently used for the first-line therapy of SCLC patients because of its better therapeutic index. Upon recurrence, topotecan is the Food and Drug Administration-approved treatment based on a phase III trial that showed no statistically significant differences in survival or response for topotecan compared with CAV (cyclophosphamide/doxorubicin/vincristine) but a better disease-related symptom improvement compared to baseline favoring the topoisomerase I inhibitor. Newer agents, with novel mechanisms of action, have shown activity against SCLC and are being tested in many different combinations. Among these agents, gemcitabine has attractive mechanisms of action and toxicity profile. Gemcitabine is a pyrimidine nucleoside antimetabolite, analogue to cytosine arabinoside, which through incorporation into the DNA leads to inhibition of DNA synthesis and cytotoxicity. As a single agent, gemcitabine has modest activity against SCLC. However, like with many other drugs, response rates improve when gemcitabine is used in combination regimens. Phase II and III studies of combinations with classic drugs for the management of SCLC patients such as cisplatin and/or etoposide and gemcitabine demonstrate comparable results to those of standard therapies. The gemcitabine/paclitaxel and gemcitabine/topoisomerase I inhibitor combinations are also of great interest, and preliminary results in previously treated patients are promising. The proper role of gemcitabine in the treatment of patients with SCLC awaits future testing in randomized phase III trials.
Clinical Lung Cancer 02/2003; 4 Suppl 2:S56-63. · 2.94 Impact Factor
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ABSTRACT: Non-small-cell lung cancer is the leading cause of cancer-related deaths in the United States. Chemotherapy has been shown to improve survival and quality of life in patients with advanced disease when compared to best supportive care. Of the commonly used therapies, platinum in combination with gemcitabine, taxanes, and vinorelbine offers superior activity to single-agent platinum or older platinum combinations. In addition, single-agent gemcitabine or single-agent paclitaxel has resulted in lower survival compared to each in combination with carboplatin in 2 recently reported phase III trials. However, among themselves new doublets have shown no improvement in survival, and treatment has traditionally been chosen based on convenience and toxicity rather than efficacy. The combination of gemcitabine and irinotecan has demonstrated promising results in preclinical studies. In this review, the data available on the combination of gemcitabine and irinotecan in phase I and phase II trials are discussed.
Clinical Lung Cancer 12/2002; 4 Suppl 1:S26-9. · 2.94 Impact Factor
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ABSTRACT: Cardiotoxicity is a rare but well-documented adverse effect of 5-fluorouracil (5-FU). The underlying cause of this side effect of 5-FU is uncertain.
We present a case report of a 63-year-old man treated for metastatic colon cancer who experienced chest pain while being treated with the FOLFIRI regimen. This case report documents coronary artery spasm on catheterization observed with the continuous infusion of 5-FU.
Cardiac catheterization obtained within 36 hours of the onset of chest pain revealed marked coronary vasospasm in the obtuse marginal coronary artery and a right coronary artery with a critical obstructive atherosclerotic plaque. Electrocardiogram revealed the myocardium area associated with the event was diffuse rather than localized to the right coronary artery.
This observation supports the vasospastic hypothesis for 5-FU-induced angina. Although rare, this type of cardiotoxicity with 5-FU is a potentially lethal side effect. Therapy with 5-FU should be discontinued and patients should be promptly treated.
Cancer control: journal of the Moffitt Cancer Center 11(1):46-9.
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George R Simon,
John C Ruckdeschel,
Charles Williams,
Alan Cantor,
Alberto Chiappori, Caio M Rocha Lima,
Scott Antonia,
Eric Haura,
Henry Wagner,
Lary Robinson,
Eric Sommers,
Michael Alberts,
Gerold Bepler
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ABSTRACT: We conducted an analysis of gefitinib in patients with advanced non-small-cell lung cancer (NSCLC) to assess the antitumor efficacy of this epidermal growth factor receptor tyrosine kinase inhibitor.
Our single-center, prospective landmark analysis included 183 patients with advanced NSCLC who received 250 mg of gefitinib orally once daily in an expanded-use program at our institution. Thirty-three of the 183 patients were previously untreated. The patients included in this analysis had all received at least 12 weeks of gefitinib.
The objective tumor response rate was 3.8%, but an additional 53.5% of patients experienced clinically meaningful disease stabilization. Median progression-free survival time was 3.6 months, and median overall survival time was 8.8 months. The 1-year survival rate for the entire cohort was 35%. Predictors of longer survival included female gender, adenocarcinoma or bronchoalveolar carcinoma histology, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea.
In this single-center experience, gefitinib demonstrated clinically significant antitumor activity and provided good palliation in a predominantly pretreated group of patients. Our results, which are likely to be reproducible in a community setting, demonstrated a 1-year survival rate of 35% in a cohort of patients who were able to take the drug for at least 12 weeks.
Cancer control: journal of the Moffitt Cancer Center 10(5):388-95.
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ABSTRACT: Colorectal cancer (CRC) is common in North America. Metastatic disease is present at diagnosis in 30% of the patients, and approximately half of early-stage patients will eventually present with metastatic disease. Until recently, few chemotherapy options were available to treat metastatic CRC.
The authors review the results of recent clinical trials and the design of ongoing trials in the management of patients with metastatic colorectal cancer.
Fluorouracil (5-FU) with leucovorin (LV) modulation has a marginal but positive effect on survival in those patients. The recent incorporation of irinotecan (CPT-11) and oxaliplatin for the management of advanced CRC has generated further improvement in survival. The development of oral fluoropyrimidines, mimicking continuous infusion 5-FU, is convenient. In randomized trials, capecitabine was equally effective to bolus 5-FU and LV in the management of metastatic CRC.
Recently completed or ongoing clinical trials to study novel targeting agents have initiated a new era of drug development. Anti-angiogenesis drugs, tyrosine kinase inhibitors, and epidermal growth factor blockers are among this new generation of agents with encouraging preliminary data. Randomized trials will determine the impact of these newer agents on survival and quality of life of patients with metastatic CRC.
Cancer control: journal of the Moffitt Cancer Center 10(3):224-38.
