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Modulation of Dose Intensity in Aerodigestive Tract Cancers: Strategies to Reduce ToxicityAdvances in diagnostic and therapeutic radiology and a better understanding of cell biology are being applied in practical ways to modulate treatment morbidity. Conformal radiotherapy targets the cancer precisely and can be combined with new systemically administered radiosensitizers.
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An Argument Against Routine Use of Radiotherapy for Ductal Carcinoma In SituWhy does the debate over theappropriate treatment ofductal carcinoma in situ(DCIS) continue? Three widely publicizedmulti-institutional randomizedtrials have addressed this question,[1-4]and all have reached largely the sameconclusion. Radiation therapy reducesthe risk of local recurrence of DCISby approximately 50%. Despite thisfact, a significant percentage of DCISpatients (50% or more in many settings)in consultation with their cliniciansopt to undergo excision aloneand forgo radiotherapy.
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Commentary (Kwok/Patchell): Radiation Therapy in the Management of Brain Metastases From Renal Cell CarcinomaBrain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
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High-Dose Chemotherapy With Autologous Stem Cell Rescue in the Outpatient SettingOutpatient bone marrow transplant (BMT) strategies, as reviewed by Dix and Geller, have evolved for various reasons—from social to medical. If high-dose approaches are to become a viable treatment for common cancers, such as breast cancer, the refinement of transplants to a “kinder and gentler” approach is essential.
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Palliative Care and Oncology Partnerships in Real PracticeThis article addresses the practical application of palliative care (PC) in the outpatient oncology setting.
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UFT/Leucovorin vs 5-FU/Leucovorin in Colon CancerAdjuvant chemotherapy has been shown to alter the natural history of resected colon cancer. Two regimens (fluorouracil [5-FU] plus leucovorin and 5-FU plus levamisole) have been found to prolong disease-free survival and overall survival in affected patients.
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Chemotherapy for Treatment of Grade II GliomasIn this article, we provide a brief overview of the management of grade II astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas-the three most heavily encountered and studied of the low-grade gliomas.
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Harnessing the Immunomodulatory Effects of Radiation TherapyIn this article, we discuss radiation’s immunomodulatory effects, with particular attention to the impact of dose and fractionation on the antitumoral response.
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Face-Off: Award Presentation CeremonyFollowing a spirited debate, Joshua K. Sabari, MD, presents the winning team with the coveted title of victors of this CancerNetwork® Face-Off event.
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Irinotecan/Cisplatin Followed by 5-FU/ Paclitaxel/Radiotherapy and Surgery in Esophageal CancerLocal-regional carcinoma of the esophagus is often diagnosed inadvanced stages because the diagnosis is established when symptomsare severe. The prognosis of patients with local-regional carcinoma ofthe esophagus continues to be grim. While preoperative chemoradiotherapyincreases the fraction of patients who achieve pathologiccomplete response, that percentage is approximately 25%. In an attemptto increase the number of patients with either no cancer in the surgicalspecimen or only microscopic cancer, we adopted a three-step strategy.The current study utilized up to two 6-week cycles of induction chemotherapywith irinotecan (CPT-11, Camptosar) and cisplatin as step 1.This was followed by concurrent radiotherapy and chemotherapy withcontinuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Oncethe patients recovered from chemoradiotherapy, a preoperative evaluationwas performed and surgery was attempted. All patients signed aninformed consent prior to their participation on the study. A total of 43patients were enrolled. The baseline endoscopic ultrasonography revealedthat 36 patients had a T3 tumor, five patients had a T2 tumor, andtwo had a T1 tumor. Twenty-seven patients had node-positive cancer(N1). Thirty-nine (91%) of the 43 patients underwent surgery; all hadan R0 (curative) resection. A pathologic complete response was noted in12 of the 39 patients. In addition, 17 patients had only microscopic(< 10%) viable cancer in the specimen. Therefore, a significant pathologicresponse was seen in 29 (74%) of 39 taken to surgery or 29 (67%)of all 43 patients enrolled on the study. With a median follow up beyond25 months, 20 patients remain alive and 12 patients remain free ofcancer. Our preliminary data suggest that the proportion of patientswith significant pathologic response can be increased by using thethree-step strategy.
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Adjuvant Treatment of Stage IB NSCLC: The Problem of Stage Subset HeterogeneityStage IB non–small-cell lung carcinoma (NSCLC) represents a subset of early-stage, resectable NSCLC, usually treated with curative intent, but with historically modest 5-year survival rates ranging from 40% to 67% with surgical resection alone.[1,2] Disappointingly, modern adjuvant chemotherapy trials including stage IB patients have shown little evidence of chemotherapeutic benefit.
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Alternative Dosing Schedules for IrinotecanMost of the clinical experience with irinotecan (CPT-11 [Camptosar]) has been with either a weekly or an every-3-week schedule. Recent phase I trials have explored new routes and schedules of administration. One approach
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Mesa Considers Next Steps With Pacritinib in MyelofibrosisRuben Mesa, MD, spoke about why pacritinib in the treatment of myelofibrosis is beneficial.
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Momelotinib Will ‘Make an Immediate Impact’ in Myelofibrosis With AnemiaWith the approval of momelotinib by the FDA, the updated use for its role in myelofibrosis will potentially change clinical practice, according to Ruben Mesa, MD.
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Best Practices in the Management of Newly Diagnosed Multiple Myeloma Patients Who Will Not Undergo TransplantNo survival advantage of autologous stem cell transplantation (ASCT) has been documented for patients older than 65 years, and in the era of thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide (Revlimid), ASCT has a diminished role in the front-line treatment of older patients with myeloma.
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Oropharyngeal Mucositis in Cancer TherapyOropharyngeal mucositis hasbeen reported as the mostbothersome side effect by patientsundergoing myeloablative regimens,and it remains a therapy-limitingtoxicity of radiation and chemotherapyfor head and neck cancer. JoelEpstein and Mark Schubert providean informative review of progressmade over more than a decade of researchon the pathophysiology andmanagement of oropharyngeal mucositisin patients undergoing cancertreatment.
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The Timing of Breast Cancer Surgery During the Menstrual CycleA number of recent studies have suggested that survival among premenopausal women after primary treatment of breast cancer may be affected by the estimated hormonal milieu at the time of surgery, especially in those with
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The Best Treatment for Diffuse Large B-Cell Lymphoma: A German PerspectiveWhile some improvement was achieved by adding etoposide and shortening the treatment intervals from 3 to 2 weeks (CHOEP-14), best results in young good-prognosis patients (age-adjusted International Prognostic Index [IPI] = 0,1) have been achieved with six cycles of CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone)-like chemotherapy in combination with the anti-CD20 antibody rituximab (Rituxan). The role of additional radiotherapy in this setting remains to be determined. With this approach, 2-year eventfree survival rates of > 90% and overall survival of > 95% can be achieved in a very favorable subgroup (patients without IPI risk factor and no bulky disease), while further improvement is warranted for the less favorable subgroup (event-free survival only 77%). For young poorprognosis patients (age-adjusted IPI ≥ 2), the 5-year survival is around 50%, and progress has not been convincingly and specifically demonstrated in these patients. Ongoing studies will show whether dose-dense conventional or high-dose chemotherapy regimens requiring stem cell support in combination with rituximab will result in similar improvements of outcome as has been reported recently for young patients with good-prognosis aggressive lymphoma. In elderly patients, CHOP interval reduction from 3 to 2 weeks (CHOP-14) and the addition of rituximab to CHOP-21 achieved similar improvements in outcome. The ongoing RICOVER-60 (rituximab with CHOP over 60) trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) evaluates whether the combination of both approaches (R-CHOP-14) can further improve the prognosis of elderly patients.
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Optimal Combination With PUVA: Rationale and Clinical Trial UpdateCutaneous T-cell lymphoma (CTCL) is relatively benign in its early stages, but survival rates decrease dramatically as the disease progresses. As no curative therapies are currently available, the goal of therapy is preventing or delaying progression from early disease stages while minimizing long-term toxicity. No single agent, including psoralen plus ultraviolet A (PUVA), can control disease progression fully, so combination therapy is needed to improve response rates. In addition, low-dose combination therapy may improve treatment safety and tolerability. A combination of PUVA and interferon (IFN)α in early disease has been shown to be effective and well tolerated. Likewise, small studies of PUVA and bexarotene (Targretin) indicate good efficacy for this combination. Reduced doses of these combinations may also be effective as maintenance therapies following complete remission. Other treatment combinations shown to be effective in early disease stages include bexarotene with IFNα, and bexarotene with denileukin diftitox (Ontak). In advanced stages of CTCL, liposomal-encapsulated doxorubicin or extracorporeal photopheresis may be combined with bexarotene or IFNα.
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Managing Nausea and Vomiting in Patients With Cancer: What WorksThis article will discuss the approach to and management of both treatment-related and non–treatment-related nausea and vomiting in cancer patients.
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Recurrent EGFR-Mutated Non–Small Cell Lung Cancer Discovered by Abnormal Mammogram: Adjuvant/Frontline Metastatic Management OptionsABSTRACT: Breast metastasis from extramammary malignancy is rare, with a reported incidence rate of 0.4% to 1.3% in the published literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. Here, we report a very rare case of metastatic EGFR-mutated non–small cell lung cancer (NSCLC) in the breast detected by screening mammography. The patient had initially been diagnosed with a clinical stage IIIA NSCLC and had been treated with neoadjuvant chemoradiation followed by curative-intent surgery. Several interesting aspects of the case, along with a discussion of evolving adjuvant and frontline metastatic management options in EGFR-mutated NSCLC, will be presented.
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Changing Treatment Paradigms for Brain Metastases From Melanoma-Part 2: When and How to Use the New Systemic AgentsIn this article, we provide an overview of the currently available systemic agents, including immunotherapeutic agents and targeted tyrosine kinase inhibitors. We also provide a practical management algorithm to guide the practicing oncologist in the use of both of these new therapies and the more traditional local treatments.
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Weekly Irinotecan and Concurrent Radiation Therapy for Stage III Unresectable NSCLCIn preclinical studies, the topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) has demonstrated activity as a radiosensitizer, probably due to its ability to inhibit potentially lethal radiation damage repair. We conducted a
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Paclitaxel, Carboplatin, and Radiation Therapy for Non-Small-Cell Lung CancerPreclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated
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More on Futile Care: Feelings of Abandonment, Confusion, and Wishful ThinkingKhatcheressian and coauthors’ article about futile care in oncology addressed an important but uncommonly discussed aspect of oncology.[1] There are several other points that were not brought up in the excellent discussion.
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Radiotherapy in Small-Cell Lung CancerGanti and colleagues have provided a brief review on the diagnosis of small-cell lung cancer (SCLC) and the roles of chemotherapy and surgery in its management. Notably, in the past three decades, the most significant progress in the treatment of SCLC has mainly involved the use of radiotherapy. Thus, to complement their assessment, we will provide an overview of the role of radiation in the management of limited-stage and extensive-stage SCLC.
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Irinotecan/Gemcitabine Followed by Twice-Weekly Gemcitabine/Radiation in Locally Advanced Pancreatic CancerEarly clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.
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The Management of Early Ovarian CancerApproximately one third of patients with epithelial ovarian cancer present with localized or early-stage disease. Prognostic features identify certain subsets of patients with good risk characteristics who do not require adjuvant
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Commentary (Cruciani/Portenoy)-Opioid Rotation in Cancer Patients: Pros and ConsOpioid rotation is now consideredstandard practice in themanagement of cancer pain.The rationale for the approach hasbeen well summarized by Estfan andcolleagues. Rotation should be viewedas one strategy among many to dealwith patients who demonstrate relativelypoor responsiveness to an opioid.[1] Application of well acceptedclinical guidelines for opioid administration,beginning with those originallypromulgated by the WorldHealth Organization,[1] emphasizethe need to individualize the opioiddose through a process of gradualdose titration, irrespective of the specificdrug. Most cancer patients attainan adequate balance betweenanalgesia and side effects, at leastinitially. Some, however, experiencetreatment-limiting toxicity, the sinequa non of “poor responsiveness.”This response reflects an outcome thatis related to a specific drug, route ofadministration, set of patient-relatedvariables, and time.
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Magnetic Resonance Imaging of the Abdomen: Applications in the Oncology PatientCross-sectional imaging of the abdomen in oncology patients presents unique challenges and opportunities. A close working relationship between the oncologist and radiologist is essential for the exchange of the clinical and
