Sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide for resectable high-risk breast cancer: feasibility and efficacy.

PURPOSE: Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) as adjuvant therapy. METHODS: Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m2 x 3, then paclitaxel 250 mg/m2/24 hours x 3, and then cyclophosphamide 3.0 g/m2 x 3; all doses were given with subcutaneous injections of 5 microg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. RESULTS: Between March 1993 and June 1994, we enrolled 42 patients. The median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 25), and the median tumor size was 3.0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease-free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. CONCLUSION: Dose-dense sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.

A global perspective on nurses' Internet access and information utilization.

PURPOSE/OBJECTIVES: To describe a global perspective of nurses accessing the Internet and using electronic information to improve cancer care. DATA SOURCES: Literature, electronic online sources, and personal experience. DATA SYNTHESIS: Nurses outside the United States encounter a number of barriers when accessing information and communicating electronically, including cultural differences, educational differences, limited access to computers and Internet services, technical and government barriers, financial difficulties, language barriers, healthcare system differences, and limited assistance and training. ONS Online has attempted to develop and strengthen relationships among nursing groups in other countries. CONCLUSIONS: Although many barriers exist for nurses outside the United States, an increasing interest is occurring in networking via the Internet and using electronic information to improve cancer care. IMPLICATIONS FOR NURSING PRACTICE: As barriers slowly are broken down and computer and Internet access increases in Europe and other countries, oncology nurses will be able to provide higher quality care to their patients with cancer. ONS Online is a quality resource that nurses outside the United States can access to develop links with oncology nursing colleagues and exchange information to enhance cancer care throughout the world.

Phase II study of semisynthetic paclitaxel in metastatic breast cancer.

The aim of this phase II study was to characterise the efficacy and toxicity of semisynthetic paclitaxel in patients with metastatic breast cancer. Eligible patients had measurable disease and had been treated with one prior chemotherapy regimen either as adjuvant or for metastatic disease. Semisynthetic paclitaxel was given at a dose of 175 mg/m2 over 3 h every 21 days with dexamethasone, cimetidine and diphenhydramine premedications. 31 patients were entered. All were evaluable for toxicity. 30 patients were evaluable for response because 1 patient was lost to follow-up after receiving one cycle. One patient achieved a complete response and 10 patients achieved partial responses for an overall response rate (CR + PR) of 37% (95% confidence interval 20-56%). 17 patients (55%) experienced at least one episode of grade 3 or 4 neutropenia. There were two episodes of febrile neutropenia complicating 155 cycles of therapy. One of these resulted in a treatment-related death in a patient with pulmonary metastasis. 3 patients required dose reductions for grade 3 sensory neuropathy. Our study shows that the antitumour activity and toxic effects of semisynthetic paclitaxel appear to be identical to the naturally occurring product.

Sequential adjuvant therapy: the Memorial Sloan-Kettering Cancer Center experience.

Adjuvant chemotherapy has a real but modest impact on the disease-free and overall survival of patients with breast cancer. Recent attempts to improve its effectiveness have focused on dose intensity and new agents. Sequential therapy maximized dose intensity while limiting overlapping toxicity. Sequential therapy using doxorubicin followed by cyclophosphamide/methotrexate/5-fluorouracil (CMF) has been found superior in patients with high-risk resectable breast cancer. The novel chemotherapy agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is now known to be highly active in advanced breast cancer and appears to be clinically non-cross-resistant with doxorubicin. Therefore, this drug is being studied as a component of the next generation of adjuvant chemotherapy regimens. The most appropriate way to incorporate paclitaxel has not yet been defined, but its concurrent administration with other agents has, in some cases, been troublesome. Based on the demonstrated advantage of the sequential plan for doxorubicin and CMF, we conducted a series of pilot trials testing sequential high-dose therapy. Initially, we studied multiple cycles of doxorubicin followed by cyclophosphamide; we later added paclitaxel to this regimen. These phase II studies demonstrate the feasibility of sequential therapy with doxorubicin, paclitaxel, and cyclophosphamide, and early disease-free survival results are promising. Cooperative group projects are under way or planned to further define the activity of these regimens.

Adjusting the dose of intravenous ondansetron plus dexamethasone to the emetogenic potential of the chemotherapy regimen.

PURPOSE: This pilot, open-label study evaluates the antiemetic efficacy and safety of a single 20-mg intravenous (IV) dose of dexamethasone combined with a single IV dose of ondansetron (32, 24, or 8 mg) in patients receiving highly emetogenic (HE), moderately high emetogenic (MHE), or moderately emetogenic (ME) chemotherapy, respectively. PATIENTS AND METHODS: One hundred forty-six patients received a single 20-mg IV dose of dexamethasone over 15 minutes beginning 45 minutes before chemotherapy and either a single 32-, 24-, or 8-mg IV dose of ondansetron over 15 minutes beginning 30 minutes before chemotherapy. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 24 hours after chemotherapy. RESULTS: Complete response (no emetic episodes) was noted in 72% (95% confidence interval [CI], 60% to 84%), 88% (95% CI, 79% to 97%), and 77% (95% CI, 63% to 92%) of patients in the HE, MHE, and ME categories, respectively. The proportion of patients who experienced no nausea on the posttreatment assessment was 51% (95% CI, 37% to 64%), 69% (95% CI, 56% to 81%), and 47% (95% CI, 29% to 65%), respectively. The antiemetic regimens were all well tolerated. The proportion of patients with any drug-related adverse events did not vary across the three study groups despite the range of ondansetron doses and variety of chemotherapy regimens. Mild headache was noted in 28% of patients. Other adverse events, all of which were noted in fewer than 10% of patients, included lightheadedness, fatigue, dizziness, and constipation. CONCLUSION: A single IV dose of either 8, 24, or 32 mg of ondansetron combined with a single 20-mg IV dose of dexamethasone resulted in good control of acute emesis across a wide spectrum of chemotherapy regimens. Nausea control proved somewhat more difficult, with approximately 50% of patients in the HE and ME emetogenic categories experiencing some degree of nausea. The results of our pilot study suggest that adjusting the dose of ondansetron to the intrinsic emetogenicity of the chemotherapy regimen permits a more efficient use of ondansetron while maintaining good antiemetic control. Such an approach appears worthy of further investigation.

An overview of the relationship between alkylating agents and therapy-related acute nonlymphocytic leukemia.

Patients with therapy-related acute nonlymphocytic leukemia present many challenges to health care professionals, yet it is only through the success of cancer management that we have uncovered this rare and unfortunate issue of survivorship. Oncology nurses have been at the forefront of symptom management, pain management, and other important issues in the care of cancer patients, and with a broader understanding can also emerge as key players in the identification and management of patients with second malignancies.

Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study.

The initial (prevalence) radiologic and cytologic screening for lung cancer in the Mayo Clinic study (Mayo Lung Project) involved 10,933 outpatients. All were men at high risk for lung cancer, but none were suspected of having it when they entered the Mayo Clinic. Screening identified 91 lung cancers (8.3 per 1,000 screened). Nearly two thirds of the prevalence lung cancers were detected by chest roentgenography alone. Half of these cancers were resected. Only a fifth of the cancers were detected by sputum cytologic examination alone; however, all but 1 of these were resected. Compared with a group of lung cancers encountered in contemporary clinical practice at the Mayo Clinic, the prevalence cancers were more than twice as likely to be (1) resectable, (2) postsurgical Stage I or II (AJCC), and (3) associated with survival 5 yr after treatment.

Roentgenographically occult lung cancer. A ten-year experience.

During the past 10 years, 54 patients, all men, were found to have roentgenographically occult lung cancer. The mean age was 61 years (range 45 to 76 years). All patients had abnormal findings on sputum cytologic study (carcinoma in 41 patients and squamous cell atypia in 13). The cancer was localized by bronchoscopy in all patients (range one to five examinations, mean 1.5). Seventy-five percent of the tumors were localized within 169 days of the abnormal sputum cytologic examination. Pulmonary resection for cure was performed in all patients: lobectomy in 38, pneumonectomy in nine, and bilobectomy in seven. Operative mortality was 5.6% (three patients). Fifty-eight cancers were resected, all squamous cell carcinomas (two had a component of large cell cancer). Tumor TNM classification (AJC) was TIS N0 M0 in 19 patients, T1 N0 M0 in 25, T1 N1 M0 in five, T2 N1 M0 in four, and T3 N0 M0 in one. Overall 5 year actuarial survival rate (lung cancer deaths only) was 90%. Five-year survival rate for the 44 patients with TIS N0 M0 and T1 N0 M0 neoplasms was 91%. Currently, 21 patients have died, but only 10 of lung cancer. Subsequent additional lung cancer developed in 12 patients (22%). Eleven of these patients had a second primary squamous lung cancer, six of which again were occult. We conclude that patients with occult lung cancer have a strong likelihood of long-term survival if treated early. Close surveillance is indicated because of the high incidence of a second primary lung cancer.

Lung cancer detected during a screening program using four-month chest radiographs.

Ninety-two lung cancers were detected in the Mayo Lung Project in patients undergoing chest radiography every four months for screening. Fifty patients had a peripheral nodule, 16 had a perihilar nodule, 20 had hilar or mediastinal enlargement, and six had pneumonitis. The peripheral cancers grew slowly. Ninety per cent were visible in retrospect for months or even years. Despite this, 70% of the peripheral cancers were classified as postsurgical American Joint Committee (AJC) Stage 1. The central cancers grew rapidly, usually presenting as hilar or mediastinal enlargements after normal findings on the previous radiograph obtained four months earlier. Most were classified as AJC Stage 3 tumors.

Survival of patients surgically treated for stage I lung cancer.

When the TNM staging system of the American Joint Committee (AJC) for Cancer Staging and End-Results Reporting was applied to 3,912 patients seen during a 6 year period at the Mayo Clinic, 624 (16%) fulfilled the criteria for postsurgical pathological Stage I non-small cell bronchogenic carcinoma. Of these 624 patients, 129 were excluded from further survival analysis for various reasons. The remaining 495 consisted of two groups: 350 patients who were enrolled within 30 days into a prospective postoperative 4 monthly follow-up program and 145 patients who were enrolled later or were followed less frequently. Because no significant difference was noted in survival rates between these groups, data were pooled. Of the combined group of 495 patients, 84% survived lung cancer for 2 years and 69% of 5 years (actuarial estimation). The survival of patients classified T1 N0 M0 (91% alive at 2 years and 80% at 5 years) is so good that it seems unlikely that adjuvant therapy in this group could demonstrate improved survival. In addition to TNM classification, age at operation, sex, and extent of operation were important determinants of survival.

Some results of screening for early lung cancer.

Screening for lung cancer is somewhat controversial in that very few evaluations of the screening process have been made, and even fewer have involved the use of concomitant, unscreened controls. This report of the Mayo Lung Project provides evaluation of a randomly selected 4500 clinic patients, offered screening for lung cancer at four-month intervals for six years. Another 4500 randomly selected controls not offered screening were merely observed. Good screening is defined, the Mayo project is evaluated, and puzzling results are presented and discussed. From the screened group, 98 new cases of lung cancer have been detected, 67 by study screening and 31 by spontaneous reporting of symptoms (15) or by x-ray examinations (16) done in other than study circumstances. From the controls, 64 new lung cancer cases have been detected, 43 by symptoms and 1 by other methods. Lung cancer mortality is 39 for study patients and 41 for controls. There is thus no evidence at this time that early case finding hs decreased mortality from lung cancer.