Randomized trial to evaluate the addition of tamoxifen to cyclophosphamide, 5-fluorouracil, prednisone adjuvant therapy in premenopausal women with node-positive breast cancer

A randomized clinical trial was performed to determine if the addition of hormonal therapy with tamoxifen to a combination chemotherapy regimen was superior to the chemotherapy alone for adjuvant treatment of premenopausal women after mastectomy for node-positive breast cancer. The chemotherapy regimen utilized consisted of cyclophosphamide (C), 5-fluorouracil (F), and prednisone (P), and the doses employed were: C, 150 mg/m2 IV days 1 to 5; F, 300 mg/m2 IV days 1 to 5; and P, 10 mg orally three times daily on days 1 to 7. A total of ten courses of therapy, given every 6 weeks, was planned. Tamoxifen (T) was given at a dose of 10 mg twice daily and was stopped 6 weeks after the last course of CFP. Four hundred patients are fully eligible and evaluable. With a median observation time of 5.3 years, the proportion of recurrences on each arm were: CFP, 95 of 202 (47%); CFPT, 77 of 198 (39%). The relapse-free survival distribution for CFPT was superior to that for CFP, at a borderline level of significance (two-sided P = 0.06). When significant prognostic factors were considered in covariate analysis, CFPT was not significantly better than CFP (P = 0.43). This marked change in level was due to imbalance in several factors not considered in stratification. Currently, 31% of CFP and 25% of CFPT patients have died, and although there is a slight separation of the survival curves in favor of CFPT, the difference is not significant (P = 0.21). Analysis within receptor subsets also showed no significant advantage for the addition of tamoxifen. This study does not establish a significant advantage for the concurrent administration of tamoxifen with the CFP regimen. It does, however, clearly demonstrate the importance of examination of clinically important prognostic factors, even those not utilized in stratification, and consideration of these factors in covariate analysis if imbalances are present.     

Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer

A randomized clinical trial was performed to determine if combination hormonal therapy with tamoxifen (TAM) and fluoxymesterone (FLU) was more efficacious than TAM alone for the treatment of postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 TAM patients (42%) and 63 of 119 TAM plus FLU patients (53%) (one-sided P = .05). Time to disease progression distributions were better for TAM plus FLU (median, 350 days v 199 days), but the log rank test only approached statistical significance (one-sided P = .07). Duration of response and survival distributions were similar between the two treatment arms. Toxicities, in terms of androgenic side effects, were greater on the TAM plus FLU regimen. Fifty-two patients are evaluable for response with FLU following TAM and 21 (40%) have achieved a response. We conclude that the advantages in terms of response rate and time to progression observed with TAM plus FLU probably represent a biological effect, but are not of sufficient magnitude to justify the routine clinical use of this combination given the lack of survival advantage and side effects encountered.     

Increased incidence of breast carcinoma in patients with irradiation for post-partum mastitis: a screening situation.

In Rochester, New York, 606 women were treated with ionizing radiation for post-partum mastitis, mostly between 1940 and 1955. Two-thirds of all breasts were treated, the average dose per breast being 377 rads (at 2.5 cm breast depth). Mammographic examinations were performed on 265 of these women still residing in this vicinity. Two nonpalpable carcinomas (with no axillary node metastases) were found in the twelve breast lesions that have been biopsied. Some of the biopsies revealed premalignant changes. It is recommended that women in this high-risk category have close medical supervision, as well as periodic mammographic evaluation, and that the importance of periodic breast self-examinations should be emphasized.     

The perception of temporally segmented vowels and consonant-vowel syllables

The minimum initial-portion durations required by listeners for the correct identification of spoken isolated vowels and consonant-vowel (CV) syllables were determined. Eight vowels [see text] and 64 CVs comprised of each of eight consonants [see text] in combination with each of the eight vowels were used. Segments consisted of the initial 10 to 150 milliseconds of each stimulus in 10-msec steps. The major findings were (1) clues for better than change correct identification of tongue advancement and tongue height values for isolated vowels occur within the first 10 msec of the stimuli whereas approximately 30 msec of the stimuli are needed for the tense-lax feature to reach threshold, (2) clues for better than chance correct identification of place of articulation for the stop consonants are found within the initial 10 msec of the CVs whereas approximately 22 msec are needed for the voicing threshold to reach threshold, and (3) the threshold of voicing increases from front to back place of articulation for the stop consonants. The implications of the findings are discussed.     

Prevalence of suspected periodontal pathogens identified using ELISA in adolescents of differing ethnic origins

Abstract The aim of this study was to determine the prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in a group of adolescents and investigate the association of these organisms with various clinical parameters. A total of 527, 11-13-year-old children, of whom 333 (63%) were white Caucasian, 187 (35%) Indo-Pakistani and 7 (1%) Afro-Caribbean, participated in the study. Subgingival plaque samples, collected from the mesio-buccal of both upper first permanent molars using sterile paper points, were stored in phosphate buffered saline with 0.01% thiomersal and analysed for the presence of A. actinomycetemcomitans, P. gingivalis and P. intermedia using ELISA. The mesio-buccal sites of both upper 1st permanent molars were also examined and the presence/absence of supragingival plaque, subgingival calculus, bleeding on probing and pocket depths greater than 3 mm were recorded. The % of white Caucasian children in whom the monoclonal antibody identified at least 1 site with A. actinomycetemcomitans, P. gingivalis and P. intermedia were 4%, 3% and 2%, respectively, and for Indo-Pakistanis were 3%, 17% and 2%. The difference for P. gingivalis was statistically significant (p < 0.001). The associations between the clinical parameters and the 3 organisms were considered separately for both upper first molar sites. The prevalence of P. gingivalis was higher for sites with subgingival calculus, pockets >3 mm and bleeding on probing (p < 0.001).     

A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.