Curr. Oncol., Volume 17, Issue 4 (August 2010) – 19 articles

Ductal carcinoma in situ (dcis) in a young man is rarely reported. Our patient, a 25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He has a strong history of cancer on both the maternal and paternal sides of his family, including breast and lung (maternal) and melanoma, colon, and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on paternal genetic testing. The patient was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gynecomastia and dcis were discovered. To date, only 4 cases of gynecomastia and dcis have been described in younger male patients. Because only 30%–50% of patients with dcis eventually develop invasive cancer in the subsequent 10–20 years, dcis prevalence in the general population may be higher than predicted. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be, and physicians must remain cautious of cancer in young men with gynecomastia. Full article

The review considers management strategies for malignant melanoma metastatic to the larynx. This rare clinical entity lacks clear treatment recommendations because extirpative surgery can often result in severe functional debilitation in patients with limited life expectancy. Here, we report a case of melanoma metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma. The patient was treated with partial laryngectomy and local radiation therapy. The rationale for treatment decisions and for surgical and radiotherapeutic techniques and the associated literature are discussed. Full article

Temozolomide (tmz) is an oral alkylating agent used during concurrent and adjuvant chemotherapy for newly diagnosed glioblastoma multiforme. Temozolomide is generally well tolerated and improves survival; however, severe adverse events have occasionally been reported. Here, we report the case of a patient who developed aplastic anemia with related complications in the setting of concurrent tmz treatment with radiotherapy. This case illustrates that aplastic anemia is a rare side effect of tmz that can occur relatively early in the course of concurrent chemotherapy, and underscores the importance of clinician awareness of this potentially devastating side effect. Full article

Melanoma is the most lethal form of skin malignancy because of its aggressive behaviour. In advanced disease, interferon alfa can be used as adjuvant therapy. However, this therapy is not free of side effects. We present a case of severe Raynaud syndrome and digital necrosis induced by interferon alfa in a patient with melanoma. Pathogenic mechanisms are discussed. Full article

Radiation recall is a well-known phenomenon that involves the “recall” of an acute inflammatory reaction in a previously irradiated region after administration of certain drugs. The most common type of radiation recall is radiation recall dermatitis, which involves the reoccurrence of an acute inflammatory skin reaction in previously irradiated skin. Most radiation recall reactions are attributable to chemotherapeutic agents. One previously reported case of radiation recall dermatitis occurred after administration of an antibiotic. The present case report is the second of radiation recall dermatitis involving an antibiotic: azithromycin. Full article

The 5th annual Bone and The Oncologist New Updates (BONUS 5) conference, held at the National Arts Center, Ottawa, April 8–9, 2010, focused on innovative research into the mechanisms and consequences of increased bone turnover in the benign and metastatic settings alike. This year there was also a debate over the controversial use of bisphosphonates as an adjuvant treatment in patients with early-stage breast cancer. This meeting report highlights a few of the topics presented. Full article

Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on comparing agents and approaches that, in phase i and ii trials, suggest efficacy. These future phase iii randomized controlled trials must clearly distinguish between preventive and management strategies for radiation-induced dermatitis. Only then can evidence-based guidelines be developed, with the hope of standardizing the approach across centres and of improving the prevention and management of radiation-induced dermatitis. Full article

Objective: Using an interview-guided survey, our descriptive study aimed to document the extent to which cancer patients perceive they are involved in making treatment decisions and the factors that influence patient involvement. Patients and methods: Our study enrolled patients from a Canadian ambulatory oncology program who were undergoing chemotherapy or radiation therapy, or both, for cancer. The adapted Control Preferences Scale was used to survey perceived and preferred roles in decision-making. The study survey also included items from the Decisional Conflict Scale and the Preparation for Decision-Making Scale. Results: Of 192 participants, 98 (51%) perceived that they were offered treatment choices. Of those 98, 47 (48%) thought that the options were presented equally. Compared with the patients not offered choices, those who were given choices were less passive (4% vs. 29%, p < 0.001) and more satisfied (100% vs. 95%, p < 0.03) in decision-making. Participants whose preferred and perceived roles were different would have preferred more involvement in decision-making. To attain the preferred involvement, patients wanted to receive more information on treatment options, to be given a choice, to have more discussion with the health care team, and to have providers better listen to their needs. Conclusions: Only half of surveyed patients thought that they were offered choices for their cancer treatment. When offered choices, patients were more active in decision-making. Further initiatives are required to determine approaches for supporting patients with cancer so that they can be more involved in decision-making. Full article

Objective: Our phase I study prospectively evaluated quality of life (QOL) in patients undergoing adjuvant chemoradiation for gastric adenocarcinoma. Methods: Thirty-three patients receiving radiotherapy (45 Gy in 25 fractions), together with 12 weeks of infusional 5-fluorouacil and escalating doses of cisplatin every 2 weeks, completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 at five time points: baseline, completion of radiation, 4 weeks after completion of radiation, 6–12 months after completion of chemoradiation, and 2–3 years after completion of chemoradiation. Results: Mean age of the patients was 56 years (range: 31–77 years); 55% of the patients were male. Median followup was 2.7 years (range: 0.3–5 years). The 3-year overall survival was 83%. Five patients experienced dose-limiting toxicity (DLT). Median scores on global QOL and on the social, role, emotional, nausea and vomiting, and fatigue scales showed clinically and statistically significant worsening at completion of radiation. Statistical but not clinical worsening was found for the physical and appetite scales. By 6–12 months, no subscale showed a difference, on average, from the baseline score. However, up to 45% of the patients remained below baseline on at least 1 subscale. Patients with DLT had worse scores on the emotional and the nausea and vomiting scales. Scores for global QOL and for nausea and vomiting were significantly associated with chemotherapy dose. Conclusions: During chemoradiation, QOL is impaired. Although most scores return to baseline, recovery may take 6–12 months, and subscale scores remain below baseline in a significant proportion of patients. Full article

Giant cell tumour (GCT) of bone is a locally aggressive benign tumour. It can, however, undergo dedifferentiation, either de novo or secondarily after local recurrence or radiation. Whether spontaneously occurring or induced by previous irradiation, this malignant transformation is typically defined as a high-grade anaplastic sarcoma devoid of giant cells. Dedifferentiation of GCT into low-grade-appearing sarcoma has not been reported yet. Here, we describe the first case of dedifferentiated GCT in the appearance of low-grade fibroblastic osteogenic sarcoma with distant bone metastases. This disease progression occurred without previous irradiation. We confirm the aggressive behaviour of this tumour despite the deceptively bland appearance of the malignant component. We also alert others to the importance of recognizing this rare histology to avoid underdiagnosis and subsequent undertreatment. Full article

Introduction: A growing number of psychosocial interventions are being offered to cancer patients during and after their medical treatment. Here, we examined whether Mindfulness-Based Stress Reduction (MBSR), a stress management course, helps women to cope better with stress and illness once their breast cancer treatment is completed. Our aim was to understand how MBSR may benefit those who participate in the course. Methods: Our cohort study enrolled 59 women in an 8-week mbsr program. They completed “before and after” questionnaires pertaining to outcomes (stress, depression, medical symptoms) and process variables (mindfulness, coping with illness, sense of coherence). Paired t-tests examined changes from before to after the mbsr course. Changes in mindfulness were correlated with changes in post-MBSR variables, and a regression analysis examined which variables contributed to a reduction in stress after program participation. Results: Adherence to the program was 91%. Participants reported significant reductions in stress (p < 0.0001), depression (p < 0.0001), and medical symptoms (p < 0.0001), and significant improvements in mindfulness (p < 0.0001), coping with illness (p < 0.0001), and sense of coherence (p < 0.0001). Changes in mindfulness were significantly related to changes in depression, stress, emotional coping, and sense of coherence. Increases in mindfulness and sense of coherence predicted reductions in stress. Conclusions: It appears that learning how to be mindful is beneficial for women after their treatment for breast cancer. Full article

Although many people welcome the recent move by the United States to give its Food and Drug Administration (FDA) the authority to regulate the content of tobacco, some worry that such regulation constitutes unwarranted interference with the freedom of competent adult tobacco consumers. The concern for protecting the autonomy of individuals is valuable indeed, but given the highly addictive nature of tobacco products (and especially the nicotine in tobacco products), the continued use of tobacco by smokers cannot —without straining credulity—be said to be autonomous. This fact, combined with a proper construal of the fda’s role and an appreciation of the substantial morbidity and mortality associated with tobacco use, makes a strong case for content regulation. Full article

Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma are opening new options for treatment. Phase III trials of cetuximab, an antibody directed against the epidermal growth factor receptor (EGFR) have demonstrated benefit in the locally advanced and metastatic settings. Recognizing the importance of emerging therapies, Cancer Care Ontario published guideline recommendations for EGFR-targeted therapy in stage III and IV head-and-neck cancer. The present paper takes a further look at the population for whom an offer of cetuximab therapy may be appropriate. Full article

Introduction: With the widespread use of sequential anthracycline/taxane–based chemotherapy for early-stage breast cancer, clinicians are becoming rapidly aware of toxicities associated with those regimens. Despite the low incidence reported in the literature of significant arthralgia and myalgia with those regimens, it is clinically evident that a substantial proportion of patients develop such toxicities. We performed a pilot study to investigate the extent of this problem. Patients and Methods: Patients who had received prior adjuvant or neoadjuvant chemotherapy [doxorubicin–cyclophosphamide followed by paclitaxel (AC-T), doxorubicin–cyclophosphamide followed by docetaxel (AC-D), or 5-fluourouracil–epirubicin–cyclophosphamide followed by docetaxel (FEC-D)] completed a retrospective outcomes-based survey. The survey utilized the Functional Assessment of Cancer Therapy–Taxane Scale, the Memorial Symptom Assessment Scale, and a modified Brief Pain Inventory. Results: Interviews were conducted with 82 patients. Interviewees had received AC-T (43%), FEC-D (43%), and AC-D (14%). Pain as a side effect of either the anthracycline or the taxane chemotherapy was reported by 87% of patients. Most of the patients (79%) indicated that their worst pain occurred during the taxane component of treatment. Compared with paclitaxel, docetaxel was reported to cause more pain. Narcotics for pain management were required by 35 of 82 patients (43%). Conclusions: A significant number of patients receiving sequential anthracycline/taxane–based chemotherapy for early-stage breast cancer experience pain, particularly during the taxane component. Prospective patient-reported outcome assessments are needed to help individualize treatment interventions and to improve symptom management in this population. Full article

Objective: This phase I study aimed to determine the maximal tolerated dose of cisplatin administered every 2 weeks with infusional 5-fluorouracil (5FU) and concurrent radiation therapy (RT) in patients after complete resection of gastric adenocarcinoma. Methods: Patients with resected stage IB to IV (M0) gastric adenocarcinoma were treated with 12 weeks of infusional 5FU (200 mg/m² daily) and with RT (45 Gy in 25 fractions starting on day 16). Cisplatin was administered in escalating doses (0, 20, 30, and 40 mg/m²) in weeks 1, 3, 5, and 7. In the final cohort, patients received an additional dose of cisplatin (40 mg/m²) in week 9. Results: Among the 34 patients [median age: 56 years (range: 31–77 years)] who were assessable for toxicity, 5 experienced dose-limiting toxicities: 1 sepsis (cohort 1), 1 fatigue (cohort 2), 3 upper gastrointestinal toxicity (1 in cohort 2, 2 in cohort 5). Cohort 5 exceeded the maximal tolerated dose. Median follow-up was 2.5 years (range: 0.3–5 years). The 3-year overall and relapse-free survival rates were 86% and 71% respectively; median survival was not reached. Conclusions: Cisplatin was well tolerated in combination with infusional 5FU and RT, showing promising activity in the adjuvant treatment of gastric cancer. Infusional 5FU 200 mg/m² daily for 12 weeks with cisplatin 40 mg/m² in weeks 1, 3, 5, and 7 and with concurrent RT 45 Gy in 25 fractions, starting at day 16, is being explored in a phase II study at our institution. Full article

Breast cancer positive for HER2 (human epidermal growth factor receptor 2) is associated with a poor prognosis for patients with both early-stage and metastatic breast cancer. Trastuzumab has been shown to be effective and is now considered the standard of care for early-stage patients with HER2-positive breast cancer. In that population, trastuzumab has been studied in six randomized clinical trials. Overall, use of this agent leads to a significant reduction in risk of disease recurrence and improvement in overall survival. Despite the strong evidence for the use of trastuzumab in managing HER2-positive early breast cancer (EBC), a number of clinical controversies remain. The authors of this paper undertook a review of the available scientific literature on adjuvant trastuzumab to produce practical considerations from Canadian oncologists. The panel focused their discussion on five key areas: (1) Management of node-negative disease with tumours 1 cm or smaller in size; (2) Management of HER2-positive EBC across the spectrum of the disease (that is, nodal and steroid hormone receptor status, tumour size); (3) Timing of trastuzumab therapy with chemotherapy for early-stage disease: concurrent or sequential; (4) Treatment duration of trastuzumab for EBC; (5) The role of non-anthracycline trastuzumab-based regimens. Full article

Background: Multiple myeloma is an incurable malignancy. Since the late 1990s, its management has changed with the introduction of novel agents. Thalidomide, which is often called a “novel” therapy, has significantly prolonged survival in multiple myeloma and is considered worldwide to be part of standard of care in this disease. However, thalidomide is not approved in Canada, leading to problems with drug access for patients. Methods: Our study surveyed Canadian hematologists on their thalidomide prescribing practices and difficulties with drug access. We address some of the ethical issues facing patients and their doctors who are unable to obtain or afford the drug, and who therefore resort to alternative means such as illegal importation. Results: Of the 411 Canadian hematologists contacted, 122 completed the survey, 97 reported that they did not treat myeloma, and 192 did not respond. Assuming that all non-responders treat myeloma, our estimated overall response rate from physicians who treat this disease was 39%. Survey participants indicated that, in Canada, access to thalidomide is a major issue for physicians and myeloma patients alike, and that 81% of respondents are dissatisfied or very dissatisfied with the drug access process. Many physicians felt that the special access process for thalidomide is unduly onerous, influences treatment decisions, and invades patient privacy. We found that 20% of physicians were unaware of the legal implications of obtaining thalidomide from other countries and that at least 23% overtly or covertly support patients in obtaining the drug from a non-Health-Canada-approved source. Conclusions: The current lack of access to thalidomide in Canada is a concerning problem for patients and health care providers dealing with myeloma. Regulatory changes at the federal level (Health Canada) need to be re-examined to promptly resolve this issue. Full article

Question: Is sunitinib malate—marketed as Sutent (Pfizer Canada, Kirkland, QC)—superior to placebo or other interventions for primary outcomes of interest in adult patients with gastrointestinal stromal tumour (GIST) who have developed resistance or who exhibit intolerance to imatinib mesylate (IM)? Background: In patients with resectable disease, surgery is the mainstay of treatment for GIST; in patients with unresectable or metastatic disease, the tyrosine kinase inhibitor IM is the therapy of choice. However, some patients have primary resistance or intolerance to IM, or they progress after optimal exposure (including an escalated dose). Here, we review the evidence for treating IM-resistant GIST with sunitinib malate. Methods: Studies of sunitinib malate were identified through MEDLINE, EMBASE, the Cochrane Library databases, and Web sites of guideline organizations. Outcomes of interest included time to progression, progression-free survival, overall survival, and toxicity. Results: One phase iii randomized controlled trial, and one abstract and presentation describing that trial, served as the evidentiary base for this clinical practice guideline. Trial data confidently show that both time to progression and progression-free survival are highly statistically significant (p < 0.0001) in favour of sunitinib malate over placebo. Overall survival was improved with sunitinib malate (hazard ratio: 0.49; 95% confidence interval: 0.29 to 0.83; p = 0.007; absolute difference in weeks not reported). The most frequent of all adverse effects (experienced in greater proportion by patients on sunitinib malate) were grades 1 and 2 leucopenia (52% vs. 5% with placebo), neutropenia (43% vs. 4%), and thrombocytopenia (36% vs. 4%). Grade 3 hematologic adverse events were also reported more frequently in the sunitinib malate group, including leucopenia (4% vs. 0%), neutropenia (8% vs. 4%), lymphopenia (9% vs. 2%), and thrombocytopenia (4% vs. 0%). Toxicity comparisons did not include p values. The incidence of grades 1–3 fatigue was greater for the sunitinib malate group (34% vs. 22% with placebo). Other grade 3 nonhematologic treatment-related adverse events that occurred more frequently on sunitinib malate included hand–foot syndrome (4% vs. 0%), diarrhea (3% vs. 0%), and hypertension (3% vs. 0%). No grade 4 adverse events were observed. Conclusions: In the target population, sunitinib malate is the recommended option for second-line therapy of metastatic GIST. Full article