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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 181 records · Page 10Linked to original sources
PubMed1990

Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a randomized clinical trial to determine whether tamoxifen (TAM) plus chemotherapy is more effective than TAM alone in improving disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of positive-node, TAM-responsive patients aged greater than or equal to 50 years. Women were randomized among three treatment groups: (1) TAM alone, (2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and TAM (ACT), or (3) melphalan (L-PAM), fluorouracil (5-FU), and TAM (PFT). The PFT arm was later modified so that new patients also received Adriamycin (PAFT). Findings from 1,124 eligible patients through 3 years of follow-up indicated a significantly better DFS for ACT-treated patients than for those receiving TAM alone (84% v 67%; P = .0004). An advantage in DDFS and S was also observed after ACT therapy (83% v 73% [P = .04 in the former] and 93% v 85% [P = .04 in the latter]). Both the DFS and DDFS of PAFT-treated patients were better than in those treated by TAM alone (83% v 66%, P = .0002 and 85% v 73%, P = .003). PFT patients also fared better in DFS and DDFS than TAM patients (81% v 72%, P = .07 and 85% v 74%, P = .02). Odds ratios consistently favored the three TAM-plus-chemotherapy groups. No significant S advantage is as yet evident in favor of the PAFT or PFT groups. Of importance is the failure of these studies to demonstrate an unfavorable interaction between the drug regimens used and the TAM, which was administered simultaneously. The findings related to the use of PAFT and PFT are of more biologic than clinical significance since L-PAM is rarely used in the treatment of breast cancer. The major conclusion from this study is the observance of a better outcome in positive-node breast cancer patients aged greater than or equal to 50 years from the use of postoperative prolonged TAM and short-course AC therapy (completed in 63 days) than from prolonged TAM therapy alone.

Aged↗
PubMed1990

Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.

Adenocarcinoma↗
PubMed1990

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The inwardly pointing knee. An unrecognized problem of external rotational malalignment.

Twelve patients with inwardly pointing knees had chronic knee pain and disability suggestive of patellofemoral subluxation. None had responded well to conservative measures or surgical correction at the level of the soft tissues. Their pattern of limb alignment was studied roentgenographically and was found to differ significantly from the control group of 49 healthy young adults. The deformities primarily related to the tibia were external tibial torsion, excess varus angulation of the tibial plateau, and varus knees. Angulation of the femoral condyles was normal and femoral anteversion did not appear to contribute significantly to the deformity. Surgery in seven cases (nine knees) was by derotation valgus Maquet osteotomy of the tibia and lateral release realignment of the patellae. Outcome assessments after a three-year follow-up period (five knees) were excellent. Early results on the remaining cases were satisfactory.

Adolescent↗
PubMed1990

A model of cooperation between complementary and allopathic medicine in a primary care setting.

This paper describes an acupuncture and osteopathy service offered free of charge to patients at a National Health Service general practice. The background to the setting up of this service, its organization, funding, aims and philosophy, and the ethical and legal implications for the general practitioners whose patients are treated by complementary therapists are discussed. This service provides a model of cooperation between allopathic and complementary medicine in a primary care setting and could be copied elsewhere.

Acupuncture Therapy↗
PubMed1989

Dukes' classification revisited. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01).

The relative prognostic value of the Dukes, Astler, and Coller and TNM staging systems was evaluated for 745 pathologically evaluable patients with rectal cancer enrolled in protocol R-01 of the National Surgical Adjuvant Breast and Bowel Projects. All three methods were found to be highly interrelated. However, the magnitude and consistency of prognostic discrimination among stages was best exhibited by the Dukes' and TNM systems. Survival was comparable among patients with Astler and Coller A and B1 and TNM T1N0M0 and T2N0M0 lesions. Since neither method improved on the predictability noted in Dukes' A cases it is suggested that the use of confusing subscripts is unnecessary. On the other hand, striking prognostic discrimination was observed when Dukes' C cases were subdivided according to depth of tumor penetration as proposed by Astler and Coller and designated as C1 and C2. Multivariate analyses revealed this feature to be independent of number of nodal metastases (1-4 versus 5+ positive), their site (near or far from the growth), or degree of tumor differentiation. The site of nodal metastases appeared to be related to numbers of nodal metastases rather than site per se. Considerations of the findings indicate that the Dukes' staging method is the simplest and most consistent algorithm related to prognosis. The only modification that would enhance its value in this regard would be the subdivision of C cases according to the criteria of Astler and Coller rather than that proposed by Dukes himself.

Aged↗
PubMed1989

In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma.

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.

Adult↗
PubMed1989

Systemic therapy in patients with node-negative breast cancer. A commentary based on two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials.

OBJECTIVE: To determine whether in the previous National Surgical Adjuvant Breast and Bowel Project (NSABP) studies of node-negative breast cancer there were either cohorts of patients with a prognosis favorable enough to preclude using systemic therapy or subsets of patients who failed to benefit from the treatments. DESIGN: Randomized clinical trials with stratification after surgery. SETTING: NSABP trials at institutions in the United States and Canada. PATIENTS: Data were collected on 731 eligible patients (Protocol B-13) with estrogen-receptor-negative tumors who randomly received either no therapy after surgery or sequential methotrexate and fluorouracil (M----F) followed by leucovorin. Data were also collected on 2834 patients (Protocol B-14) with estrogen-receptor-positive tumors who randomly received either placebo or tamoxifen treatment. The percentage of patients surviving disease-free was determined through 4 years of follow-up using life-table estimates. INTERVENTIONS: Protocol B-13 patients received 12 courses of M----F given intravenously on days 1 and 8 every 4 weeks. Leucovorin therapy was begun 24 hours after M----F administration. Protocol B-14 patients received 5-year treatment with either tamoxifen (10 mg twice daily by mouth) or placebo. RESULTS: When the outcome of untreated patients in either trial was related to the stratification variables, women were found to have a disease-free survival of less than 80% through 4 years of follow-up. This percentage is apt to decrease because the probability of treatment failure increases with time. In both trials, all subsets of women benefited from M----F or tamoxifen therapy. CONCLUSIONS: The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen-receptor-positive tumors was poor enough to justify systemic treatment. The benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth-stimulating factor in mice.

This report indicates that not only does the preoperative administration of cyclophosphamide or radiation prevent the kinetic changes observed in a distant tumor focus following tumor removal but that the preoperative administration of the antiestrogen tamoxifen and the luteinizing hormone-releasing hormone analogue Zoladex are equally effective in that regard. It also provides evidence indicating that serum obtained from mice treated with those therapies when transferred to a recipient bearing a tumor of a similar type to that in the donor fails to stimulate DNA synthesis in the tumor of the recipient. In contrast, an increase in labeling index occurs following transfer of serum obtained following tumor removal from untreated mice. Moreover, when tumor-bearing mice were treated by each of the four modalities prior to receiving serum obtained from untreated donors following removal of a tumor, no kinetic changes were observed in the tumor of the serum recipient.

Animals↗
PubMed1989

Presence of a growth-stimulating factor in serum following primary tumor removal in mice.

The effect of removal of a primary tumor on the kinetics of cells in a metastasis was evaluated using six different tumors (C3H, MXTa, MXTb, MC54, CD8, and 3LL) which varied relative to their origin, histology, and the strain of mice in which they were carried. There was an increase in the labeling index (LI) of distant tumor focus ("metastasis") associated with the removal of each of the tumor types and unrelated to operative and anesthetic trauma. Information presented supports the presence of a serum growth factor as being responsible for the phenomenon. Serum obtained from mice following removal of a tumor, when transferred to a recipient with the same type of tumor as in the donor, resulted in an increase in the LI of the tumor. Multiple injections of serum failed to add to the increase but did prolong its presence, suggesting that there is a finite population of cells, most likely in the G1-G0 phase, which are capable of responding to the stimulating factor. The transfer of serum obtained following removal of a tumor type different from that in recipients resulted in findings which indicate that tumors producing a stimulating growth factor are those capable of responding to it. Serum obtained from animals with unremoved tumors or less than 18 h after removal failed to substantially augment the LI of tumors in recipients. It is postulated that the growth factor released by a tumor is in an inactive form which becomes activated over time. Observations indicate that medium conditioned by the growth of C3H tumor contains a growth-stimulating factor which is capable of increasing the LI of a C3H tumor in a recipient in a fashion similar to that obtained following tumor removal. That finding indicates the capability of the tumor to elaborate growth-stimulating material which may be similar to that found in serum. The findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences. They indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor(s) which can influence the outcome of a host to its tumor.

Animals↗
PubMed1989

Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer.

In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, less than or equal to 4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P less than 0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58 +/- 2.6 percent), distant-disease-free survival (65 +/- 2.6 percent), and overall survival (71 +/- 2.6 percent) that were not significantly different from those observed after total mastectomy (54 +/- 2.4 percent, 62 +/- 2.3 percent, and 71 +/- 2.4 percent, respectively). There was no significant difference in the rates of distant-disease-free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy.

Breast Neoplasms↗
PubMed1989

A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors.

We evaluated the postoperative use of sequential methotrexate and fluorouracil followed by leucovorin in 679 patients with primary breast cancer, histologically negative axillary nodes, and estrogen-receptor-negative (less than 10 fmol) tumors. No survival advantage was observed with this therapy as compared with no postoperative therapy during four years of follow-up (87 percent vs. 86 percent; P = 0.8). However, there was a significant prolongation of disease-free survival among women who received this therapy as compared with those who did not (80 percent vs. 71 percent; P = 0.003). An advantage was observed in both the patients less than or equal to 49 years old and those greater than or equal to 50. At four years, treatment failure was reduced by 24 percent in the younger group and by 50 percent in the older group. The rates of both local and regional and distant metastases were decreased. These benefits, achieved without the use of an alkylating agent, were associated with tolerable side effects. Multivariate analysis testing for potential interactions failed to identify subgroups of patients who did not benefit from the therapy. These results, although promising, do not obviate the need for additional trials to evaluate potentially better regimens of therapy, but they do suggest that sequential methotrexate-fluorouracil should be used in the control arm in such studies. Their use is also justified for the treatment of patients who refuse to participate in clinical trials, provided the patients meet the eligibility criteria of the present study. Since women with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not included in this study, we do not recommend systemic treatment for them outside of a clinical trial.

Aged↗
PubMed1989

A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.

We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen; P = 0.3). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent; P less than 0.00001). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation. The benefit was attained with a low incidence of clinically appreciable toxic effects. The magnitude of the improvement obtained does not preclude the need for future trials in which patients given tamoxifen could serve as the control group in an evaluation of potentially better therapies. Tamoxifen treatment is justified in patients who meet the eligibility criteria of the present study and who refuse to participate in those trials. Since patients with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not eligible for this study, no information is available to indicate that such patients should receive tamoxifen.

Adult↗
PubMed1989

Relative prognostic value of the Dukes and the Jass systems in rectal cancer. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01)

A comparison of the prognostic values of the Dukes and Jass systems were performed with 722 patients with rectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Projects, protocol R-01. The Jass system revealed four prognostic groups when all patients or only Dukes' B and C cases were examined; however, the magnitude of differences between groups I and II and III and IV were small. Dukes' classification, as defined in this study, revealed five prognostic groups. A statistically strong association between the Jass and Dukes systems was observed. Although histologic grade permitted further prognostic discrimination of all Dukes stages except A, only the Jass system allowed for the subdivision of C cases with up to four nodes positive for metastases. Those in that group had survival rates comparable to B cases (no nodal involvement) when scores of I and II were found. The distributions of the patients in the extremes of the Jass and Dukes systems (C2 as defined) were almost similar. The findings indicate that the Jass system is a valid prognostic method for patients with rectal carcinoma. In this material, however, it basically allowed for only two major prognostic groups whereas five were noted by the Dukes method. These results, as well as the more objective nature of Dukes' classification, warrant its continued use for prognosis and therapeutic decisions for patients with rectal cancer.

Humans↗
PubMed1989

Prognostic significance of eosinophils and mast cells in rectal cancer: findings from the National Surgical Adjuvant Breast and Bowel Project (protocol R-01).

The numbers of eosinophils and mast cells observed at the tumor border of 331 rectal cancers from patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP), protocol R-01, were correlated according to overall survival rate, as well as Dukes' stage, tumor differentiation, nodal status, degree of lymphoid and stromal reactions, sex, and age. Life table plots disclosed a significantly better overall survival rate when ten or more eosinophils per 30 oil immersion fields were found. However, the numbers of eosinophils were strongly associated with Dukes' stage and, when life table plots were adjusted for Dukes' stage, this relationship to survival rate was not evident. On the other hand, overall survival rate was significantly higher in patients in whom 0 to three mast cells per 30 oil immersion fields were found than in those patients in whom four or more mast cells were found. This relationship persisted even when life table plots were adjusted for treatment, Dukes' stage, or nodal status, and indicated that the number of mast cells further defined survival rate among patients exhibiting Dukes' A, B, and C stages. It is concluded that numbers of eosinophils and mast cells may play a role in the natural history of rectal cancer but only the latter represents a prognostic parameter independent of Dukes' stage or nodal status. The mechanism whereby mast cells may exert this effect is at present unknown.

Cell Count↗