Stephen A. Bernard

Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.

PURPOSE A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.

Incidence and duration of chemotherapy-induced nausea and vomiting in the outpatient oncology population.

Nausea and vomiting are commonly recognized side effects of chemotherapy. However, the incidence and duration of these effects have not been systematically studied in a large outpatient oncology population. This survey was conducted over two consecutive 6-week periods in the adult oncology clinics of two university teaching hospitals. The objectives were: (1) to document the incidence and duration of chemotherapy-induced nausea and vomiting; (2) to identify variables that influence nausea and vomiting; and (3) to describe patterns of antiemetic prescribing and compliance. One hundred thirty-eight completed patient-maintained diaries were returned (70% response rate). Anticipatory nausea and vomiting were reported by 9.4% and 6.5% of patients, respectively. Fifty percent and 27% of patients reported nausea and vomiting, respectively, on the day chemotherapy was administered (day 1: acute nausea and vomiting phase). Percentages fell to 22% and 11% by day three and 14% and 2.5% on day 5. Of patients who reported nausea and vomiting during the five-day period, 52% and 33% experienced nausea and vomiting, respectively, during the delayed period only (days 2 through 5: delayed emesis phase). Emetogenicity of chemotherapy significantly influenced incidence and duration of those symptoms. Sixty-seven percent of patients reported taking antiemetics on one or more days during the survey period. Of patients who reported antiemetic use, 92% reported antiemetics on day 1, 51% on day 3, and 31% on day 5. At-home antiemetic use was related to the emetogenicity of chemotherapy received. Patients who receive moderate to strong emetogens as defined in this report should receive antiemetic therapy for a minimum of three days. Increasing the dose of antiemetic prescribed both in the clinic and at home may be of benefit.

Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma of the esophagus.

BACKGROUND Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. METHODS From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant (p = 0.13), but the difference in recurrence-free survival was significant (p = 0.007). CONCLUSIONS This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

Local recurrences in patients with breast cancer at the North Carolina memorial hospital (1970–1982)

A study of predictive factors for locoregional recurrences after curative surgery for breast cancer was undertaken. Specifically, the authors wished to determine whether such recurrences correlated with either hormonal receptor status or a delay between the initial biopsy and the definitive surgery. A retrospective chart review was done on all women with breast cancer who had surgery for cure between 1970 and 1982. Factors analyzed included, among others, size of the tumor, clinical and pathologic status of the axilla, estrogen and progesterone receptors status, and delay between biopsy and definitive surgery. There were 404 patients studied. Pathologic axillary nodal status was the most important predictor of locoregional recurrence, with failures in 36 of 188 (19%) node‐positive but only 9 of 216 (4%) node‐negative patients (P 0.0001). In node‐positive patients, tumor size was a predictor of local recurrence, with failure in only 4 of 51 (8%) of tumors less than 2 cm, but in 14 of 44 (32%) of tumors greater than 6 cm (P = 0.004). Progesterone receptor (PR) status correlated with locoregional recurrence, but estrogen receptor status did not. In node‐positive women, there were 4 of 14 PR‐negative but 0 of 15 PR‐positive local failures (P = 0.017); this result has not been previously reported. The presence of palpable axillary disease was also found to be a predictor of local recurrence. Finally, no increase in locoregional recurrence could be attributed to the delay between biopsy and definitive surgery. Two new predictors for locoregional recurrence in breast cancer, not previously emphasized, are PR and clinical axillary status. Should these findings be substantiated, patients at high risk for locoregional recurrence could then be more readily identified.

Adjuvant Therapy With the Monoclonal Antibody Edrecolomab Plus Fluorouracil-Based Therapy Does Not Improve Overall Survival of Patients With Stage III Colon Cancer

PURPOSE Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. PATIENTS AND METHODS Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). RESULTS One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based therapy compared to FU-based therapy was 0.896 (95% CI, 0.752 to 1.068), which was not statistically significant (P = .220). The adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. Anaphylaxis occurred in fewer than 1% of patients receiving ED. CONCLUSION For patients with stage III colon cancer, the addition of ED to FU-based therapy had no statistically significant effect on OS.

Use of yttrium-90 microspheres in patients with advanced hepatocellular carcinoma and portal vein thrombosis.

PURPOSE Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options because of increased disease burden and diminished hepatic perfusion. Yttrium-90 ((90)Y) microspheres may be better tolerated than chemoembolization in these patients. The present study reviews the safety and efficacy of (90)Y microspheres in HCC with major PVT. MATERIALS AND METHODS A retrospective review of HCC with main (n = 10) or first-branch (n = 12) PVT treated with (90)Y microspheres (N = 22) was conducted. Cancer of the Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients having a score of 4 or greater. Imaging response at 8-12 was based on Response Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the Kaplan-Meier method. RESULTS A total of 32 microsphere treatments (26 glass, six resin) were administered to 22 patients. Common grade 1/2 toxicities included abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment hospitalizations occurred, all less than 48 hours in duration. One death occurred 10 days after therapy. The partial response rate was 8% and progressive disease was seen in 42% of patients. Stable disease was achieved in 50% of treatments. Median OS was 7 months from initial treatment. Patients with Child-Pugh class A disease had a median OS of 7.7 months; those with class B/C disease had an OS of 2.7 months (P = .01). Median OS for patients with CLIP scores of 2/3 was 7 months, versus 1.3 months for those with scores of 4/5 (P = .04). CONCLUSIONS Yttrium-90 microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. The median OS of 7 months is promising and warrants further study versus systemic therapy.

Integration of a clinical pharmacist into the hematology–oncology clinics at an academic medical center

PURPOSE The development, implementation, and early experience with a program providing clinical pharmacist services at the hematology-oncology clinics of a university teaching hospital are described. SUMMARY With funding from a university research grant and other sources, a pharmacist was hired to launch a new program addressing four goals identified in a needs assessment: (1) improved management of supportive care, (2) enhanced education of patients receiving complicated chemotherapy regimens, (3) improved efficiency in the chemotherapy infusion unit, and (4) development of an experiential learning opportunity for pharmacy students and residents. The pharmacist hired to lead the ongoing program was a state-approved clinical pharmacist practitioner (CPP) who had authority to prescribe with physician oversight under established protocols. EXPERIENCE An oncology supportive care consultation service implemented by the CPP in collaboration with a nurse and a physician served 89 new patients in its first 18 months of operation; during that period the CPP made 186 interventions and wrote 136 prescriptions. The CPP also established a chemotherapy counseling service that provided more than 900 bill-able patient education sessions over 18 months. In addition, the CPP launched an effort to increase use of a rituximab rapid-infusion protocol among eligible patients. The creation of the new oncology pharmacist position has given dozens of pharmacy students and residents a new opportunity for interaction with oncology clinic patients and other health care team members. CONCLUSION Integration of the services of a CPP into the hematology-oncology clinics has helped achieve goals set by physician, nursing, and pharmacy leaders.

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy : Comparison of ondansetron, prochlorperazine, and dexamethasone

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.

Pharmacist-Led, Interdisciplinary Model for Delivery of Supportive Care in the Ambulatory Cancer Clinic Setting

PURPOSE To describe a pharmacist-led, interdisciplinary method of care delivery begun at the University of North Carolina. We describe the characteristics of the population seen and the role of the individual members of the interdisciplinary team, and provide an early analysis of the programs impact on symptom improvement. METHODS A supportive care consultation service was begun at the University of North Carolina Hospitals to serve adult outpatients with cancer undergoing treatment or follow-up. Patients data were entered into an institutional review board-approved database to permit detailed assessments over time. Patient demographics were analyzed using descriptive statistics, medications used and changes made were noted, and symptom scores from a previously described instrument were captured and compared over time. RESULTS Patients were seen from all adult oncology services, including gynecologic, radiation, medical, and surgical. The characteristics of the population seen were similar to those of the hospital population as a whole. Most of the patients were seen for pain management, and many required a medication change. Symptom scores improved by the second visit, and the improvement was maintained. CONCLUSION We are able to demonstrate that the use of a pharmacist-led, interdisciplinary team produced an improvement in symptom scores comparable to what has been seen in the inpatient palliative care service within our institution. Projected shortages of oncology providers may be mitigated by pharmacists working in collaborative practices, with prescriptive authority, in the ambulatory oncology setting.

Ondansetron for the prevention of emesis induced by high‐dose cisplatin. A multi‐center dose‐response study

To determine a dose‐response relationship of ondansetron for the prevention of emesis induced by high‐dose cisplatin and to study the efficacy of the extended dosing schedule of ondansetron during 20 hours after cisplatin administration, 36 patients with malignant neoplasms who had not previously received chemotherapy but who were currently receiving cisplatin were treated. These patients received a six‐dose regimen of 0.01 mg/kg (low dose) or 0.18 mg/kg (high dose) of ondansetron. Seven (41%) patients in the high‐dose group had no emesis and four (24%) patients had one or two episodes. One (5%) patient in the low‐dose group had no emesis and four (21%) patients had one or two episodes. The difference in the number of emetic episodes was significant (P < 0.02). Fifty percent of the high‐dose patients reported no nausea or mild nausea, compared with 11% of the low‐dose patients. Clinical adverse events included mild, transient headache and dizziness in the high‐dose group and headache and diarrhea in the low‐dose group, with no significant laboratory abnormalities. There is a parallel relationship between the ondansetron doses and the antiemetic efficacy. The response rate for the six‐dose regimen of 0.18 mg/kg was not superior to that for the previously reported 0.18 mg/kg regimen given in a three‐dose schedule in a similar clinical setting.