Multilobular tumor of bone in the mandible of a dog.

An 8-year-old Siberian husky dog was presented for a mass involving the rostral mandible. Intraoral radiographs demonstrated diffusely irregular bone and displacement of all mandibular incisor teeth. The mass was diagnosed as a grade I multilobular tumor of bone based on incisional biopsy. A bilateral rostral mandibulectomy was performed with tumor negative margins. Oral examination at 14-months following surgery indicated normal healing with minimal side effects and no evidence of tumor recurrence.

Ellis Fischel Cancer Center: cancer care at the crossroads.

Ellis Fischel Cancer Center, the first state cancer center west of the Mississippi River, opened its doors in 1940, one year before Houston's M. D. Anderson. Ellis Fischel has been through major and challenging transitions over the years and is in the midst of another. The institution has matured, evolved and progressed to a modern, full service facility and care paradigm. Ellis Fischel has never faltered in its time-honored traditional value of serving the needs of all Missourians regardless of socioeconomic status or geographic location. We review in this paper services available at Ellis Fischel and how they are likely to change over the next five years.

Close monitoring and lifetime follow-up is optimal for patients with a history of melanoma.

Malignant melanoma, a potentially lethal form of skin cancer, is becoming more common each year in the United States and worldwide. The cure rate, however, is also increasing due to better education, earlier detection, and more effective treatment. Thus, there are more melanoma survivors who are at risk for recurrence of melanoma and also a second primary. Because there are few prospective screening and surveillance results in the medical literature, recommendations for follow-up of melanoma survivors have been based on the natural history of the disease, physical examinations, laboratory tests, and radiologic evaluations.

Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer.

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.

Pain relief at the end-of-life: a clinical guide.

Pain at the end-of-life is usually treatable, but most dying patients are under-treated and die in unnecessary pain. This brief overview will serve to describe the problem of pain at the end-of-life, define the relevant ethical, medical, scientific, and societal issues, and present an optimal pain management plan for this vulnerable and important population. The most important factor is for physicians to make pain control a matter of paramount importance in the care of dying patients.

Relieving non-pain suffering at the end-of-life.

We discuss non-pain problems at end-of-life in this paper. Management of these problems is key to ensuring relief of suffering. Much of this paper is a reiteration of the material on common physical symptoms, which is presented in module 10 of the Education for Physicians on End-of-life Care (EPEC) project of the American Medical Association in conjunction with the Robert Wood Johnson Foundation.

Melanoma reporting in Missouri.

Thorough reporting of the diagnosis and treatment of various cancers in underserved and rural communities is perhaps one of the greatest challenges to the Missouri physician. We introduce and discuss the use of a new reporting mechanism for registering melanoma cases with the Missouri Cancer Registry in an effort to assess trends in melanoma incidence, improve standards of care, and develop strategic plans for melanoma prevention and screening in the future.

Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma.

PURPOSE: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). EXPERIMENTAL DESIGN: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. RESULTS: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). CONCLUSION: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.

Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma.

PURPOSE: Elesclomol is a novel, small-molecule, oxidative stress inducer believed to exert selective cytotoxicity by increasing intracellular concentrations of reactive oxygen species, which results in cell death via mitochondrial apoptosis. We evaluated whether the addition of elesclomol to weekly paclitaxel could improve efficacy in patients with stage IV metastatic melanoma. PATIENTS AND METHODS: We randomly assigned patients with metastatic melanoma, measurable disease, and one or fewer prior chemotherapy regimens to elesclomol 213 mg/m(2) plus paclitaxel 80 mg/m(2) (E + P) or to paclitaxel 80 mg/m(2) alone at a 2:1 ratio; regimens were given as a 1-hour intravenous infusion weekly, during 3 of every 4 weeks until disease progression per Response Evaluation Criteria in Solid Tumors or death occurred. Patients who experienced progression were unblended, and patients on paclitaxel alone were permitted to cross over to E + P. The primary efficacy end point was progression-free survival (PFS); secondary end points were response rate (RR), toxicity, and overall survival (OS; analyzed post hoc). RESULTS: At 21 US sites, 53 patients were randomly assigned to E + P, and 28 patients were randomly assigned to paclitaxel. The addition of elesclomol to paclitaxel yielded a doubling of median PFS (112 v 56 days) and a 41.7% risk reduction for disease progression/death (hazard ratio, 0.583; P = .035). Respective RRs for the E + P and paclitaxel groups were 15% and 3%; median OS was 11.9 v 7.8 months. Of patients on paclitaxel alone, 19 (68%) of 28 crossed over to E + P after they experienced progression. Weekly E + P was well tolerated. CONCLUSION: E + P resulted in a statistically significant doubling of median PFS, with an acceptable toxicity profile and encouraging OS. A multinational, phase III trial (SYMMETRY) of E + P compared with paclitaxel alone in metastatic melanoma has closed.

Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma.

PURPOSE: Biochemotherapy improves responses in metastatic melanoma, but not overall survival, in randomized trials. We developed a maintenance biotherapy regimen after induction biochemotherapy in an attempt to improve durability of responses and overall survival. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naïve patients with metastatic melanoma without CNS metastases were treated at 10 melanoma centers. The biochemotherapy induction regimen included cisplatin, vinblastine, dacarbazine, decrescendo interleukin-2 (IL-2), and interferon alfa-2b with granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine support. Patients not experiencing disease progression were eligible for maintenance biotherapy with low-dose IL-2 and GM-CSF followed by intermittent pulses of decrescendo IL-2 over 12 months. Patients were observed for response, progression-free survival, toxicity, and overall survival. RESULTS: The response rate to induction biochemotherapy was 44% (95% CI, 35% to 52%; complete response, 8%; partial response, 36%; stable disease, 29%). The median number of biochemotherapy cycles was four, and the median number of maintenance biotherapy cycles was five. The median progression-free survival was 9 months, and the median survival was 13.5 months. The 12-month and 24-month survival rates were 57% and 23%, respectively. Twenty percent of patients remain alive (12 without disease), with median follow-up of 30 months (95% CI, 25+ to 45+ months). Thirty-nine percent of patients developed CNS metastases. The median times to CNS progression and death were 8 months and 5 months, respectively. CONCLUSION: Maintenance biotherapy after induction biochemotherapy seems to prolong progression-free survival and improve overall survival compared with recent multicenter trials of biochemotherapy or chemotherapy. The regimen should be studied in a randomized clinical trial in patients with advanced metastatic melanoma. CNS progression remains a formidable challenge.

A randomized phase III trial of biochemotherapy versus interferon-alpha-2b for adjuvant therapy in patients at high risk for melanoma recurrence.

The objective of this study was to compare the clinical benefit of biochemotherapy and interferon-alpha-2b (IFN) as adjuvant therapy. Biochemotherapy has higher response rates than other regimens in patients with metastatic melanoma. We conducted a randomized phase III study comparing the clinical benefit of biochemotherapy and IFN as adjuvant therapy. Patients who had undergone lymphadenectomy for melanoma metastatic to regional lymph nodes were randomly assigned to either biochemotherapy or IFN, and IFN patients were further randomized to either high-dose IFN (HDI) or intermediate-dose IFN (IDI). The primary end point was relapse-free survival (RFS); the secondary end point was overall survival (OS). The planned enrollment was 200 patients, the number required to have 80% power to detect, at a significance level of 5%, an improvement in median RFS from 18 to 36 months and an improvement in median OS from 40 to 80 months between the IFN and biochemotherapy groups. A futility analysis was performed because of slow accrual. One hundred and thirty-eight patients were enrolled - 71 in the biochemotherapy group, 34 in the HDI subgroup, and 33 in the IDI subgroup. No significant differences in median RFS or OS between the HDI and IDI subgroups were observed. With a median follow-up of 49.3 months, neither the biochemotherapy nor IFN group had reached median RFS or OS, and there were no significant differences in estimated median RFS or OS (P=0.86 and 0.45, respectively) between the two groups. Biochemotherapy is not more effective than IFN as adjuvant therapy for melanoma. These findings support early termination of this trial.

Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma.

PURPOSE: To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting. PATIENTS AND METHODS: Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy. The biochemotherapy regimen consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800 mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5. Growth factor support was administered with each cycle. RESULTS: Ninety-two patients were eligible for the study. At a median follow-up of 40.4 months, relapse-free survival and overall survival are 64% and 78%, respectively. There was a lower relapse rate and improved survival for patients with a positive sentinel lymph node compared with patients with clinically detected lymph nodes, although this difference did not reach statistical significance. Of the 50 patients with measurable disease, the overall response rate was 26%. Toxicity of the biochemotherapy was high but generally manageable. CONCLUSION: The current study has expanded the preliminary evidence on neoadjuvant biochemotherapy for stage III melanoma.

Nutritional, functional, and emotional characteristics related to fatigue in patients during and after biochemotherapy.

PURPOSE/OBJECTIVES: To test Winningham's psychobiologic entropy hypothesis in patients receiving biochemotherapy for melanoma. DESIGN: Descriptive, correlational, cross-sectional study. SETTING: Midwest cancer center. SAMPLE: 25 male and female patients who were receiving biochemotherapy or who had completed treatment 6-12 months prior. METHODS: Data were collected using a series of questionnaires and diet recall. MAIN RESEARCH VARIABLES: Fatigue, anxiety, depression, distressing symptoms, nutritional intake, and weight. FINDINGS: Moderate fatigue was significantly related to physiologic and psychological symptoms but not to nutrient intake. The sample was overweight, and a significant number of participants were obese. High caloric intakes were evident. Depression was a significant problem. CONCLUSIONS: Fatigue was not as severe as expected, but problems with responses to the fatigue scale may explain this. Nutritional status and nutrient intake were not correlated to fatigue in this sample. Activity levels were related to fatigue, and treatment reduced activity. On average, activity returned to pretreatment levels 6-12 months after treatment. Winningham's hypothesis held and will be useful for understanding fatigue in this population. IMPLICATIONS FOR NURSING: Depression needs to be assessed and treated as a side effect of biotherapy. Assessing the impact of nutrition when patients are overweight or obese is difficult. A scale specifically designed to test Winningham's hypothesis is needed.

A phase II study of biochemotherapy for advanced melanoma incorporating temozolomide, decrescendo interleukin-2 and GM-CSF.

Metastatic malignant melanoma remains a very difficult disease to treat. Previous phase II studies using biochemotherapy (combination of platinum-containing chemotherapy with IL-2 and IFNalpha) have shown response rates of about 50%. However, a site of frequent relapse is in the central nervous system (CNS). Temozolomide is an oral alkylating agent that has equivalent activity to dacarbazine, but it has the advantage of CNS penetration. We report the results of a phase II study using a novel biochemotherapy regimen containing temozolomide, cisplatin, decrescendo IL-2, IFNalpha, and GM-CSF in the treatment of stage IV melanoma. Seventy-one patients with histologically confirmed metastatic melanoma were enrolled between June 1998 and October 1999. Prior chemotherapy or IL-2 was not permitted. The median age was 54 years (range 22-72). Twenty-one patients (30%) had a history of treated brain metastases. Patients received temozolomide 150 mg/m2 orally days 1-5, cisplatin 30 mg/m2 IV days 1-3, IFNalpha 5 MU/m2 SQ on days 1-5, and IL-2 was administered in a decrescendo fashion according to the following schedule: day 1: 18 MU/m2 continuous IV infusion over 6 hours; day 2: 18 MU/m2 continuous IV infusion over 12 hours; day 3: 9 MU/m2 subcutaneously q12 hours; day 4: 4.5 MU/m2 subcutaneously x 1. Patients were also given GM-CSF 250 microg subcutaneously days 6-25. The cycles were repeated every 4 weeks. Partial responses were seen in 10 of the 71 patients (14%) with a median duration of response of 9.4 months. There were no complete responses. The median survival for all patients was 8.6 months. Further studies of this novel biochemotherapy regimen are not indicated. Other schedules that incorporate temozolomide and/or GM-CSF and further studies to define the optimal method of delivering IL-2 should be pursued.

Patients' perceptions of fatigue in response to biochemotherapy for metastatic melanoma: a preliminary study.

PURPOSE/OBJECTIVES: To explore patients' perceptions of fatigue in response to biochemotherapy treatment for metastatic melanoma. DESIGN: A descriptive-correlational, cross-sectional study. SETTING: A cancer center in the midwestern United States. SAMPLE: 12 adult patients between the ages of 28-70 who received at least one cycle of biochemotherapy treatment for metastatic melanoma (stages III and IV) from the inpatient or outpatient services of a midwestern cancer center. METHODS: A demographic data sheet and the Revised Piper Fatigue Scale (PFS) were used to collect data at a single point in time after patients received at least one cycle of biochemotherapy. FINDINGS: The majority of patients who received biochemotherapy reported severe or moderate fatigue. Female patients' total fatigue scores were higher than those of male patients. Fatigue duration varied from hours to months, with a maximum duration of 12 months after biochemotherapy treatment. All of the patients reported that the most direct causes of their fatigue were metastatic melanoma and biochemotherapy treatment. CONCLUSIONS: Patients who received biochemotherapy treatment for metastatic melanoma reported moderate to severe fatigue. Female patients experienced more intense fatigue than male patients. The findings also supported the multidimensionality of fatigue construct identified in prior fatigue studies. The four dimensions/subscales of fatigue assessed by the Revised PFS were highly correlated to total fatigue scores. IMPLICATIONS FOR NURSING: Biochemotherapy is a newer treatment modality for metastatic melanoma. Fatigue, one of the severe toxicities from biochemotherapy treatment, necessitates attention from nurses. The findings will assist nurses in teaching patients about fatigue that may be expected during or after biochemotherapy and about self-care strategies to manage fatigue.

A phase II study of neoadjuvant biochemotherapy for stage III melanoma.

BACKGROUND: Phase II studies of biochemotherapy (combining interleukin-2, interferon-alpha, and multiagent chemotherapy) have reported high response rates and a significant number of durable complete responses in patients with metastatic melanoma. METHODS: A pilot Phase II study was performed to explore the safety and activity of neoadjuvant biochemotherapy in patients with Stage III melanoma. Forty-eight patients were enrolled between April 1996 and May 1999. The median age of the patients was 46 years (range, 19-70 years). Two cycles of biochemotherapy were administered prior to and after complete lymph node dissection. Each cycle was comprised of cisplatin, 20 mg/m2 intravenously (i.v.), on Days 1-4; vinblastine, 1.6 mg/m2 i.v., on Days 1-4; dacarbazine, 800 mg/m2 i.v., on Day 1; interleukin-2, 9 x 10(6) IU/m2/day i.v. over 24 hours, on Days 1-4; and interferon-alpha, 5 x 10(6) IU/m2/day subcutaneously, on Days 1-5, every 3 weeks. Twelve patients did not have measurable disease. All patients were evaluable for toxicity and survival. RESULTS: Clinical responses were observed in 14 of 36 patients (38.9%) with measurable disease, including 13 partial responses (36.1%) and 1 complete response (2.8%). Complete pathologic responses were noted in 4 patients (11.1%). Toxicity, although severe, was manageable and typically short-lived. There were no treatment-related deaths reported. At a median follow-up of 31 months, 38 of the 48 patients (79.2%) were alive and 31 patients (64.6%) remained free of disease progression. CONCLUSIONS: Neoadjuvant biochemotherapy appears to have promising activity in patients with Stage III melanoma. A larger multicenter study currently is underway to explore this approach further.