Altruism--a coping mechanism for patients on clinical trials: a nursing perspective.

Altruism often is expressed by patients with advanced cancer as a coping mechanism and a motivational factor for participation in clinical trials. Those who participate develop a sense of hope that their life is a contribution, which may continue to live beyond their deaths.

The changing hope trajectory in patients with advanced-stage cancer: a nursing perspective.

As patients with advanced-stage cancer move from the initial diagnosis through treatment, remission, recurrence, and advanced-stage disease, the hope trajectory undergoes a dynamic transformation. By identifying the hope trajectory, nurses can help patients focus on obtainable hope objects while balancing the need to present a realistic prognosis. This, in turn, may help patients find meaning and purpose in advanced-stage cancer and facilitate realistic hope when faced with a life-threatening illness.

Iron deficiency anemia related to hereditary hemorrhagic telangiectasia: response to treatment with bevacizumab.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant condition associated with arteriovenous malformations (AVMs) or telangiectasias of the pulmonary, gastrointestinal or hepatic circulations. The authors present a case of a 52-year-old woman with a known diagnosis of HHT who presented for evaluation of anemia. She had an extensive history of iron sucrose infusions, frequent blood transfusions and hospitalizations for anemia related to gastrointestinal bleeding and epistaxis. The patient was treated with bevacizumab at a dose of 5 mg/kg infusion every 2 weeks for 4 cycles. In the next 4 months, her hemoglobin improved to 13.7 g/dL and she did not require iron or packed red blood cell transfusions for the next 8 months. Abnormal angiogenesis primarily due to mutations in the transforming growth factor ß receptor endoglin and the activin receptor-like kinases is a central contributor to the formation of AVMs in HHT. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor and therefore may be a useful treatment against AVM formation in patients with HHT. The authors do caution that therapy has to be individualized as there are no randomized trials regarding its usage in patients with HHT.

Gemcitabine/epirubicin/paclitaxel as neoadjuvant chemotherapy in locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group.

BACKGROUND: This phase II protocol of neoadjuvant chemotherapy with gemcitabine/epirubicin/paclitaxel (GET) was designed to determine the pathologic complete response (pCR) rate in the breast, clinical response rate, disease-free survival, and overall survival at 2 years as well as toxicity in patients with locally advanced breast cancer. This trial also evaluated the feasibility of tissue collection for gene-expression profiling. PATIENTS AND METHODS: Seventy-six women with stage IIB, IIIA, and IIIB breast cancer were entered into this trial. Patients received a maximum of 6 cycles of neoadjuvant GET chemotherapy every 21 days (gemcitabine 1000 mg/m2 intravenously [i.v.] on days 1 and 4, epirubicin 90 mg/m2 i.v. bolus on day 1, and paclitaxel 175 mg/m2 i.v. on day 1). After chemotherapy, patients underwent surgery and were assessed for pathologic response. RESULTS: The pCR rate among the 74 patients evaluable for efficacy was 23% (95% CI, 14%-34.2%). Adverse events among the 76 patients evaluable for toxicity included anemia requiring transfusion (14.5%), infection with grade 3/4 neutropenia (10.5%), febrile neutropenia (7.9%), and platelet transfusion (6.6%). Infectious complications occurred in 24 patients (31.6%), of whom 18.4% were in the setting of neutropenia. High-quality RNA and successful probe synthesis were obtained from all pretreatment core biopsy specimens that contained tumor cells (n=66; 88%). CONCLUSION: Neoadjuvant GET chemotherapy is an active regimen but with substantial toxicity. Tissue collection for gene-expression profiling is feasible in a multi-institutional setting.

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma: a North Central Cancer Treatment Study, N0021.

BACKGROUND: The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen. METHODS: A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m(2) intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m(2) intravenously on Day 1 on an every-21-days cycle (high-dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m(2) and epirubicin at a dose of 70 mg/m(2) with the same schedule (low-dose patient group). RESULTS: In the high-dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3-34%). The median survival was 9.3 months (95% CI, 7.4-10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0-7.6 months). In the low-dose patient group, the confirmed response rate was 7% (95% CI, 0-28%). The median survival was 5.7 months (95% CI, 4.7-8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7-5.6 months). Toxicity was moderate to severe. In the high-dose and low-dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high-dose group but worsened in the low-dose group. CONCLUSIONS: In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma.

A Phase I/II study of GTI-2040 and capecitabine in patients with renal cell carcinoma.

BACKGROUND: Fluoropyrimidine based therapy has modest activity in patients with metastatic renal carcinoma and inhibition of ribonucleotide reductase is synergistic in model systems. GTI-2040 is a 20-mer phosphorothioate oligonucleotide complimentary to the R2 component of ribonucleotide reductase that has activity in renal cancer models. METHODS: Metastatic renal carcinoma patients without prior fluoropyrimidine therapy and normal organ function were treated with oral capecitabine 880 mg/m(2) twice daily along with continuous infusion GTI-2040 starting at 148 mg/m(2)/day for 21 days, for each 28-day cycle. After completion of the phase I portion, the phase II study portion sought to rule out a null hypothesized 10% response rate versus an alternative 25% response rate utilizing alpha and beta errors of 0.05 and 0.2, respectively. GTI-2040 pharmacokinetics and effects on ribonucleotide reductase expression in peripheral mononuclear cells were evaluated in a subset of patients. RESULTS: Based on one dose limiting toxicity in nine patients in the phase I portion, the phase II portion was conducted using the previously recommended 185 mg/m(2)/day dose of GTI-2040. Twenty-six patients were enrolled in the phase II portion to obtain 18 fully evaluable for response. Only one patient, treated at a GTI 2040 dose of 185 mg/m(2)/day in the phase I portion of the protocol, responded. Toxicities and GTI-2040 pharmacokinetics were consistent with previously reported results. R2 expression in peripheral mononuclear cells was too variable for accurate interpretation. CONCLUSION: Further study of GTI-2040 and capecitabine in metastatic renal cancer at this dose and schedule is not indicated. Further study is necessary to determine whether lack of activity is due to inadequate target inhibition or inadequate effect of appropriate targeting.

Phase III comparison of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) vs. doxorubicin and cisplatin (AC) in women with advanced primary or recurrent metastatic carcinoma of the uterine endometrium.

OBJECTIVES: The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer. METHODS: Twenty-eight patients were randomly assigned to treatment with doxorubicin 30 mg/m2 + cisplatin 70 mg/m2 IV q 4 weeks vs. methotrexate 30 mg/m2 IV days 1, 15, and 22, vinblastine 3 mg/m2 IV days 2, 15, and 22, doxorubicin 30 mg/m2 IV day 2, and cisplatin 70 mg/m2 day 2 of a 4-week cycle. The trial was terminated prematurely due to slow accrual. RESULTS: Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20%) for AC and 3 CR (23%) and 3 PR (23%) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0%. No treatment-related deaths were seen. DISCUSSION: MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population.

Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252.

PURPOSE: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial. PATIENTS AND METHODS: Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m(2) dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m(2) dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity. HER2 status was confirmed by a central laboratory review. RESULTS: The overall response rate (ORR) with every-3-week therapy was 65% (90% confidence interval [CI], 51%-77%), with a median time to disease progression of 9.9 months and median overall survival (OS) time of 2.3 years. The ORR with weekly therapy was 81% (90% CI, 70%-90%), with a median time to disease progression of 13.8 months and a median OS time of 3.2 years. Hematologic and nonhematologic toxicities occurred significantly less frequently with weekly therapy versus every-3-week therapy: grade 3/4 neutropenia (52% vs. 88%); grade 3 thrombocytopenia (4% vs. 30%); and grade 3 neurosensory toxicity (2% vs. 19%), respectively. CONCLUSIONS: Every-3-week and weekly regimens of paclitaxel/carboplatin/trastuzumab are highly active in women with HER2-overexpressing MBC. However, fewer patients developed severe neutropenia, leukopenia, or thrombocytopenia with the weekly schedule.

Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both.

PURPOSE: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. PATIENTS AND METHODS: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks. RESULTS: The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. CONCLUSION: Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.

Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer.

PURPOSE: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen. PATIENTS AND METHODS: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (LV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1370 patients). RESULTS: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m2/wk). CONCLUSION: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer.

Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking.

PURPOSE: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. PARTICIPANTS AND METHODS: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. RESULTS: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P =.73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P =.12). CONCLUSION: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.

Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study.

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58.

Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6%), diarrhea (4%), arthralgia/myalgia (3%), and neurotoxicity (1%). Clinical congestive heart failure was seen in 3 patients (3.4%). Seventy-seven patients were evaluable for best response within 6 cycles of therapy. Thirteen patients (16.9%) had a complete response, 43 (55.8%) had a partial response, for an overall response rate of 72.7%. The median response duration was 23.8 months (95% CI, 16.2-37.8 months), and the median time to progression or death was 23.5 months (95% CI, 16.3-38.7 months). The median survival time was 35.6 months (95% CI, 26.6-39.4 months). The administration of ATC with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible and active. Its value in the adjuvant setting is currently under investigation.

A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia.

PURPOSE: The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination. PATIENTS AND METHODS: Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals. RESULTS: The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo. CONCLUSION: The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.