Effects of therapeutic touch on biochemical and mood indicators in women.

Previous research has shown therapeutic touch (TT) to be effective in reducing anxiety and discomfort and promoting relaxation. The present investigation experimentally evaluated the effects of TT on biochemical indicators and moods in a sample of 41 healthy female volunteers. Participants were randomly assigned to either an experimental group who received TT or to a control group who did not receive TT. Pretest and posttest urine samples were collected, and personality and mood inventories were administered across three consecutive monthly sessions. Results indicated that mood disturbance in the experimental group decreased significantly over the course of the three sessions, while the control group increased in mood disturbance over time. Specifically, experimental group participants showed significant reductions in tension, confusion, and anxiety and a significant increase in vigor across sessions. Analyses of the biochemical data indicated that TT produced a significant decrease in levels of nitric oxide in the experimental group by the third TT session. The results of the present investigation have important implications for reducing symptom distress in cancer patients undergoing chemotherapy.

Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. PATIENTS AND METHODS: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. RESULTS: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia was 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. CONCLUSION: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer.

Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group.

PURPOSE AND METHODS: By the mid 1980s, tamoxifen alone was considered standard adjuvant therapy for postmenopausal women with node-positive, estrogen receptor (ER)- or progesterone receptor (PgR)-positive breast cancer. From 1984 through 1990, 705 eligible postmenopausal women with node-positive, ER- or PgR-positive breast cancer were randomized to a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study that compared tamoxifen 30 mg by mouth daily for 2 years (TAM) versus TAM plus chemotherapy with all-intravenous cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 given every 21 days for eight cycles (CMF). RESULTS: There were no significant differences in overall survival, recurrence-free survival, locoregional recurrence-free survival, or distant recurrence-free survival between the two treatment arms. However, there was significantly greater severe toxicity, which included leukopenia (P < .0001), nausea and vomiting (P < .0001), and thromboembolic events (P < .0001), as well as significantly more mild or greater toxicity, which included thrombocytopenia (P = .04), anemia (P = .02), infection (P = .0004), mucositis (P = .0001), diarrhea (P = .0001), and neurologic toxicity (P = .006), in women who received TAM plus CMF. CONCLUSION: The addition of CMF to TAM adds no benefit and considerable toxicity in this group of women.

The Canadian experience with intensive fluorouracil, epirubicin and cyclophosphamide in patients with early stage breast cancer.

A multicentre dose-finding pilot study was conducted to determine an intensive regimen of fluorouracil (F), epirubicin (E) plus cyclophosphamide (C) [FEC] that was tolerable and acceptable to patients with node-positive operable (n = 266) or locally advanced (n = 22) breast cancer. Consecutive patients were treated with fluorouracil and epirubicin administered intravenously on days 1 and 8, in addition to cyclophosphamide orally for 14 days. Chemotherapy cycles were repeated at monthly intervals for 6 months, and dosages were increased according to a predetermined protocol. End-points were hospital admissions due to febrile neutropenia and changes in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated with doses of F = 375 mg/m2, E = 50 mg/m2 and C = 75 mg/m2 (level 1), then 42 patients received F = 500 mg/m2, E = 50 mg/m2 and C = 75 mg/m2 (level 2), 69 patients received F = 500 mg/m2, E = 60 mg/m2 and C = 75 mg/m2 (level 3), and 42 patients received F = 500 mg/m2, E = 70 mg/m2 and C = 75 mg/m2 with concurrent antibiotics (level 4). Rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4) [p = 0.002]. Accrual to level 4 was discontinued according to study protocol and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between dosage levels 3 and 3a was statistically significant (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy induced amenorrhoea in a randomised trial of adjuvant chemotherapy duration in breast cancer.

We have previously reported the results of a clinical trial in patients with stage II breast cancer which compared a 12 week chemohormonal regimen with a 36 week chemotherapy regimen. Both pre and post menopausal women were entered. The 12 week regimen was inferior both in terms of disease-free survival and overall survival. The effect of chemotherapy on menstrual function was prospectively documented in 95 of 114 premenopausal women at 3 of the 4 participating centres. 67 of the 95 women (70.5%) developed permanent amenorrhoea. There was a statistically significant difference in the rate of induced amenorrhea between the 12 week and the 36 week groups; 23/42 vs. 44/53, respectively (P = 0.003). Recurrence and mortality rates were lower in the patients who became amenorrheic; 38% vs. 57% (P = 0.03) and 18% vs. 32% (P = 0.17), respectively. Similar trends were observed within treatment groups. The effect of induced amenorrhoea on outcome was seen predominantly in patients under 40 years old. These results suggest that the induction of ovarian failure is a potential mechanism for the observed effect of adjuvant chemotherapy in these patients. The difference in the ovarian failure rates between groups may be a possible explanation for the inferiority of the 12 week regimen.

A pilot study of intensive cyclophosphamide, epirubicin and fluorouracil in patients with axillary node positive or locally advanced breast cancer.

A multicentre pilot study has been conducted to determine an intensive regimen of cyclophosphamide, epirubicin, and fluorouracil which was tolerable and acceptable to patients with node positive breast cancer. Consecutive patients with operable axillary node positive breast cancer (T1-3, N1-2, M0), 266 patients, or locally advanced breast cancer (T4), 22 patients, were treated with cyclophosphamide post-operatively for 14 days and epirubicin and fluorouracil, both intravenously on days 1 and 8. Each cycle was repeated monthly for 6 months. Dosages were increased according to predetermined guidelines. Outcome measures were admission to hospital for febrile neutropenia and change in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated at the doses of cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2, fluorouracil = 375 mg/m2 (level 1), then 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2 and fluorouracil = 500 mg/m2 (level 2), 69 patients at cyclophosphamide = 75 mg/m2, epirubicin = 60 mg/m2, and fluorouracil = 500 mg/m2 (level 3), and 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 70 mg/m2, and fluorouracil = 500 mg/m2 with concurrent antibiotics (level 4). The rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4), respectively, P = 0.002. Accrual to level 4 was discontinued according to study guidelines and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between levels 3 and 3a was statistically significant. There were no toxic deaths and 2 cases of heart failure. In conclusion, through a careful dose-finding study in patients with operable or locally advanced breast cancer, an intensive epirubicin-containing adjuvant regimen has been established which is presently being compared with standard CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy in a randomised trial. In addition, this study suggests that antibiotic prophylaxis reduces the risk of febrile neutropenia in breast cancer patients receiving intensive chemotherapy.

The effect of systemic adjuvant chemotherapy on local breast recurrence in node positive breast cancer patients treated by lumpectomy without radiation.

A randomised trial has previously been repeated in which 437 women with node positive breast cancer received either a 12-week chemohormonal regimen consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, adriamycin and tamoxifen or 36 weeks of CMFVP. The present analysis concerns the local recurrence rates for the 122 lumpectomy patients who did not receive breast irradiation. The cumulative rate of local breast recurrence was greater in the 12-week than the 36-week group, P = 0.02. Similarly, in the lumpectomy patients, the cumulative rate of distant recurrence was greater in the 12-week than the 36-week group, P = 0.04. In conclusion, our results suggest that adjuvant chemotherapy impacts on local breast recurrence in a similar manner to other sites in Stage II breast cancer patients treated by lumpectomy without radiation. Despite the use of a conventional 36-week adjuvant chemotherapy regimen, the local breast recurrence rate was substantial.

A randomized trial comparing 12 weeks versus 36 weeks of adjuvant chemotherapy in stage II breast cancer.

A randomized trial has been performed in which women with axillary node-positive breast cancer were allocated to either a short intensive 12-week chemohormonal treatment consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and tamoxifen (CMFVP plus AT) or 36 weeks of CMFVP. The median follow-up is 37 months. Of the 222 women randomized to the 12-week treatment, 113 (50.9%) have experienced either recurrence or death as compared with 90 patients (41.9%) in the 36-week treatment group. The corresponding 3-year relapse-free survivals are 55% and 64%, respectively, P = .003. Fifty-nine (26.6%) of the patients in the 12-week group have died compared with 46 (21.4%) of the 36-week group. The corresponding 3-year survival rates are 78% and 85%, respectively, P = .04. A Cox regression analysis showed an associated increased risk ratio for recurrence or death of 1.7, P = .003, and for death of 1.8, P = .017 in the 12-week treatment group compared with the 36-week group. Thus, this 12-week regimen of adjuvant chemohormonal therapy is inadequate treatment for women with axillary node-positive breast cancer; possible explanations for this inferiority are its shorter duration and/or a negative interaction of tamoxifen on the chemotherapy.

Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas.

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.

Mitoxantrone and cyclophosphamide in advanced breast cancer: a pilot study.

A trial of combination chemotherapy using mitoxantrone-cyclophosphamide was started in 1983. Sixteen patients with widely metastatic cancer of the breast, including one man, received mitoxantrone, 10 mg/m2 intravenously (IV) over 30 minutes on day 1, followed by cyclophosphamide, 200 mg/m2 by mouth (PO) daily in divided doses on days 3 to 6. It is too early to evaluate four patients at present. The remaining 12 received three or more courses of treatment, and three of these patients achieved a complete response. Another four patients went into partial remission, amounting to an overall response rate of 58%. The other evaluable patients showed stable disease with improved symptoms. Hematologic toxicity was mainly granulocytopenia, but thrombocytopenia occurred in two patients. Alopecia, nausea, and vomiting were attributed to the cyclophosphamide component of the therapy. Mitoxantrone appeared to have no cardiac toxicity. It was concluded that mitoxantrone-cyclophosphamide is an effective chemotherapeutic combination with minimal toxicity and should be further studied in larger controlled trials.

A phase I-II study of maytansine utilizing a weekly schedule.

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I-II study. Dose-limiting toxic reactions which occurred at 0.75-1.0 mg/M2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose-level of 0.5 mg/M2 in Phase I:1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at dose-level of 1.0 mg/M2. All responses were in heavily pretreated patients. pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12-24 hours.

Treatment of acute myeloblastic leukemia in adults: remission induction with a combination of cyclophosphamide, cytarabine and vincristine.

A regimen of intravenous cyclophosphamide, cytarabine and vincristine, given over a four-day period and repeated every two to three weeks, was used to treat 33 patients with acute myeloblastic leukemia. Of the 30 evaluable patients 9/18 previously untreated patients achieved complete remission and two others marked improvement, and 4/12 previously treated patients achieved complete remission. Twelve of 16 patients under the median age of 38 responded while only 3/14 patients over this age responded. There was no difference in response between those with elevated muramidase levels and those with normal levels. Three patients developed a previously unrecognized syndorme of fever, malaise, rash and orbital suffusion. Cytarabine was probably responsible.At least four courses of treatment are required before abandoning this regimen of therapy. Patients who achieve a complete remission and live for more than 150 days spend about 25% of their total survival time from diagnosis in hospital.