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Biomedical subjects

J N Ingle

Publications and source records attributed to J N Ingle.

At least 73 records · Page 4Linked to original sources
PubMed1993

Patterns of tumor relapse following mastectomy and adjuvant systemic therapy in patients with axillary lymph node-positive breast cancer. Impact of clinical, histopathologic, and flow cytometric factors.

BACKGROUND: This analysis was conducted to evaluate the impact of selected clinical, histopathologic, and flow cytometric factors on sites of initial tumor relapse after postmastectomy adjuvant systemic therapy. METHODS: Five hundred sixty-four patients with axillary node-positive breast cancer were entered in two prospectively randomized trials and received cyclophosphamide, 5-fluorouracil and prednisone with or without tamoxifen as sole adjuvant therapy. These patients were studied to assess the risk of locoregional recurrence and to identify factors that might predict tumor relapse site. RESULTS: With a median follow-up of 9.3 years, the 8-year cumulative incidences of initial locoregional or distant relapse were 20% and 35%, respectively. Pathologic tumor stage, estrogen receptor content, and number of involved axillary nodes were independent predictive factors for an increased risk of locoregional recurrence. With the exception of tumor stage, these factors also were associated with an increased risk of distant relapse so that tumor stage (T3a) remained the sole factor predictive of increased relative risk for initial locoregional (versus distant) recurrence in patients with tumor progression. Clinical and flow cytometric factors were not predictive of initial locoregional or distant relapse. CONCLUSIONS: Exploratory data analysis of two prospective trials of postmastectomy adjuvant systemic therapy has demonstrated a significant risk for initial isolated locoregional recurrence in certain patients with node-positive breast cancer. The benefit of improved locoregional tumor control in appropriately selected patients with axillary node-positive breast cancer who receive adjuvant systemic therapy requires additional investigation.

Adult↗
PubMed1993

DNA ploidy and percent S-phase as prognostic factors in node-positive breast cancer: results from patients enrolled in two prospective randomized trials.

PURPOSE AND METHODS: To help clarify the clinical utility of flow-cytometric parameters, we performed flow cytometry on archival paraffin-embedded primary breast cancers from 502 patients treated on two adjuvant chemotherapy protocols performed by the North Central Cancer Treatment Group (NCCTG) and Mayo Clinic. DNA ploidy and percent S-phase (%S) were examined in univariate and Cox model multivariate analyses along with tumor size, menopausal and estrogen receptor status, Quetelet's index (QI), number of positive nodes and nodes examined, and Fisher and nuclear grades. RESULTS: Ploidy analysis showed that 40% of tumors were DNA diploid and 60% were DNA nondiploid (12% tetraploid and 48% aneuploid). There was no difference in relapse-free survival (RFS) (P = .82) or overall survival (OS) (P = .78) between the ploidy groups. Tetraploid patients had the longest RFS and OS of any group, but this did not achieve statistical significance. The %S was computed in 98% of cases and the medians were 9.0% for all patients, 6.4% for diploid patients, and 11.7% for nondiploid patients (P < .0001). By use of a %S greater than 12.3 as a prognostic variable in a univariate analysis, there was a significant difference in the RFS (P = .02) and OS (P = .007) of patients with low- versus high-proliferative tumors. However, when the %S was adjusted for clinical characteristics in the multivariate analysis, it was not a significant factor for RFS (P = .23) or OS (P = .36). CONCLUSION: These results indicate that DNA content and %S measurements by flow cytometry are not clinically useful independent prognostic factors in women with resected node-positive breast cancer administered adjuvant chemotherapy.

Adult↗
PubMed1993

Postchemotherapy rheumatism.

PURPOSE: This report describes a previously unreported clinical phenomenon that occurs in some patients after completion of combination chemotherapy. METHODS AND RESULTS: Eight case reports are presented. Affected patients developed a syndrome of myalgias/arthralgias within several months of completing cyclophosphamide/fluorouracil (5FU)-containing adjuvant combination chemotherapy for breast cancer. These symptoms did not appear to be related to cancer recurrence or any common rheumatologic disorder. The syndrome generally resolved over several months. CONCLUSION: Postchemotherapy rheumatism is a syndrome of myalgias/arthralgias that usually develops 1 to 3 months after completion of adjuvant chemotherapy. Recognition of this syndrome can limit the need for extensive work-ups to exclude recurrent breast cancer or inflammatory rheumatologic diseases.

Adult↗
PubMed1991

DNA content flow cytometry as a prognostic factor for node-positive breast cancer. The role of multiparameter ploidy analysis and specimen sonication.

The DNA content was analyzed in paraffin-embedded material from 167 patients with node-positive breast cancer to learn whether specimen sonication and multiparameter ploidy analysis (MPPA) (using DNA content and light scatter) could improve the strength of ploidy as a prognostic variable. Sonicated specimens were found to have fewer aggregates, a lower percentage of cells in S-phase (%S) and G2M phase than the corresponding nonsonicated specimens. The results using MPPA predicted the prognosis better because they allowed detection of small aneuploid peaks in histograms classified as diploid or tetraploid using DNA content alone. Ploidy was a significant univariate factor, and patients with tetraploid tumors had the best survival. In the multivariate analysis, if other routine factors were examined preferentially, ploidy and %S did not provide additional prognostic information for survival. This study of paraffin-embedded breast cancers suggested that sonication and MPPA may improve the ploidy analysis in certain cases and that tetraploidy may be a favorable ploidy pattern in this group.

Breast Neoplasms↗
PubMed1991

A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

This trial was conducted to determine if the reported superiority of tamoxifen (TAM) plus prednisolone (PRDLN) over TAM alone in postmenopausal women with metastatic breast cancer could be corroborated. A total of 326 patients were randomized on a double-blind trial to TAM (10 mg twice daily) plus placebo or TAM plus PRDLN (5 mg twice daily). Six patients (2%) were disqualified. Considering 256 patients with measurable or evaluable disease, objective responses were seen in 48 (38%) of 126 TAM patients and 61 (47%) of 130 TAM plus PRDLN patients (chi-square, P = 0.15). Considering all 320 evaluated patients, median time to disease progression was 11 months for TAM and 10 months for TAM plus PRDLN (log rank, P = 0.81), and median survival time was 35 and 32 months, respectively (P = 0.40). Covariate analyses showed no significant association between treatment and outcome. Weight gain and edema were significantly greater with TAM plus PRDLN. The addition of PRDLN to TAM is not advocated for the management of postmenopausal women with metastatic breast cancer.

Adult↗
PubMed1991

Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis.

A randomized trial was performed to determine if therapy with tamoxifen (TAM) plus fluoxymesterone (FLU) was more efficacious than TAM alone for 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 (42%) TAM patients and 64 of 119 (54%) TAM plus FLU patients (two-sided P = 0.07). Time to disease progression was better for TAM plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03). Duration of response and survival were similar in the two treatment arms. Among 97 patients with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there were highly significant advantages for treatment with TAM plus FLU in both response rate and time to progression. Of particular note is that in this patient group TAM plus FLU showed a survival advantage (Cox model, P = 0.05). Although these data require confirmation in a prospective randomized trial, they suggest that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone in elderly women with ER of 10 fmol or greater.

Adult↗
PubMed1991

Systemic adjuvant therapy in women with resected node-negative breast cancer.

Currently, the role of adjuvant systemic therapy in women with node-negative breast cancer is being determined. Several studies of adjuvant hormonal therapy and adjuvant chemotherapy have demonstrated a moderate reduction in the risk of recurrence in the treated patients. With relatively limited follow-up, however, overall survival has not improved with use of adjuvant therapy. The use of prognostic factors to select those patients at highest risk for relapse is an active area of oncologic research. The decision to recommend adjuvant therapy necessitates assessment of the probability of recurrence, the expected reduction of risk with adjuvant therapy, the toxic effects of therapy, and the influence of treatment on the patient's overall quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

5-Fluorouracil plus leucovorin in women with metastatic breast cancer. A phase II study.

Because leucovorin increases the antitumor activity of 5-fluorouracil (5-FU) in multiple tumor model systems, we performed a clinical trial to evaluate this combination in women who had received one or no prior chemotherapy regimens for metastatic breast cancer. Thirty-six women with measurable metastatic disease were treated with five consecutive days of i.v. leucovorin, 500 mg/m2/day infused over 30 min, followed 1 h later by i.v. bolus 5-FU, 375 mg/m2/day. Repeat cycles were planned at 4-week intervals. Tumor regression occurred in 10 of 36 patients (28%; 95% confidence interval, 14-45%) with a median time to disease progression (TTP) of 8.7 months (range 3.2-16.8 months) in the responding patients. The median TTP and survival for all patients were 3.0 and 12.4 months, respectively. Among 30 patients who had received prior 5-FU, tumor regressions were seen in seven (23%; 95% confidence interval 10-42%). The major dose-limiting toxicity in this study was mucositis, affecting 89% of the patients. Other toxicities were tolerable in the majority of patients. Although the role of leucovorin in breast cancer clinical practice remains undefined, the data from this trial support the hypothesis that leucovorin enhances the cytotoxic activity of 5-FU against human breast cancer.

Adult↗
PubMed1991

A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer.

Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer.

Adult↗
PubMed1990

Identification of putative nonfunctional steroid receptors in breast and endometrial cancer.

A nuclear binding assay was developed for the purpose of having available a more predictive assay for hormone responsiveness in human cancers. The BNB assay identified specific and saturable steroid nuclear binding in human target tissues and human carcinomas. When the BNB assay was applied to a large set of breast and endometrial carcinomas, we speculate that nonfunctional receptors were detected in 20%-50% of the patients who were receptor-positive by the DCC assay. Lastly, as responsiveness to hormonal therapy in these cancer patients becomes known, the predictive value of the BNB assay can be established.

Biopsy↗
PubMed1990

Evaluation of trilostane plus hydrocortisone in women with metastatic breast cancer and prior hormonal therapy exposure.

Trilostane, which causes a perturbation of adrenal steroidogenesis, was studied in combination with hydrocortisone in 32 women with progressive metastatic breast cancer. Trilostane was administered orally at a dosage level of 240 mg four times daily after escalation over the first 10 days from 60 mg four times daily. Hydrocortisone was given orally at doses of 10 mg at 8 a.m. and 5 p.m. and 20 mg at bedtime. Patients must have been postmenopausal (81%) or previously castrated (19%), had a response to the hormonal treatment just prior to study (81%) or a positive estrogen receptor at time of entry on study (41%), and a measurable indicator lesion. The number of prior hormonal therapies was 1 in 19 patients (59%), 2 in 12 patients (38%), and 3 in 1 patient (3%), respectively. Twelve patients (38%) achieved an objective response, and a 95% confidence interval for this result is from 21 to 56%. The median time to disease progression was 140 days, median duration of response was 278 days, and median survival was 556 days. Common toxicities included lethargy, lightheadedness, diarrhea, and abdominal discomfort. Eleven patients required a dosage reduction, usually because of gastrointestinal side effects, and one additional patient had the trilostane discontinued because of leukopenia. We conclude that the combination of trilostane plus hydrocortisone appears to have definite antitumor activity in women with metastatic breast cancer who have characteristics favorable for response to hormonal therapy.

Adult↗
PubMed1990

Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer.

Six hundred forty-six women with node-positive breast cancer from two prospective, randomized, adjuvant breast cancer trials were evaluated for changes in weight during and after receiving 60 weeks of chemotherapy, chemohormonal therapy, or observation. The median weight change in the 545 patients remaining on protocol at 60 weeks for observed postmenopausal patients was +1.8 kg, for treated postmenopausal patients +3.6 kg, and for treated premenopausal patients +5.9 kg (P less than .001). After a median follow-up of 6.6 years, premenopausal women who gained more than the median weight at 60 weeks had a risk of relapse 1.5 times greater (covariate P = .17) and a risk of death 1.6 times greater (covariate P = .04) than premenopausal women who had gained less than the median weight. In the postmenopausal patients, the trend for inferior relapse-free and overall survival in those who gained more than the median weight at 60 weeks was not significant (P = .05). We conclude that, relative to observation, adjuvant chemotherapy is associated with greater weight gain in node-positive, postmenopausal breast cancer patients; the amount of weight gain appears greater for premenopausal than postmenopausal women, and in premenopausal women, excessive weight gain may be associated with an increase in relapse and cancer-related deaths in the selected patients who show no evidence of recurrence during 60 weeks of adjuvant chemotherapy. This last point must be interpreted with caution because of the exploratory nature of the analyses.

Adult↗
PubMed1989

Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer.

A randomized trial was performed to determine relative efficacy and toxicity of two first-line combination chemotherapy regimens in women with metastatic breast cancer: CFP (cyclophosphamide, 5-fluorouracil, prednisone) and CMFP (cyclophosphamide, 5-fluorouracil, methotrexate, prednisone). Both regimens have reported efficacy in this setting but differ in dosages and scheduling of the agents they have in common. Three hundred thirty-six women with no prior chemotherapy for metastatic disease were eligible and evaluable, and 309 had either measurable or evaluable disease and were assessable for objective response. Responses were seen in 65 of 153 (42%) on CFP and 83 of 156 (53%) on CMFP (two-sided P = 0.06). Median durations of response were 7.1 months for CFP and 8.5 months for CMFP (log-rank, two-sided P = 0.67). Considering all 336 patients, the median times to disease progression were 4.7 months for CFP and 6.2 months for CMFP (log-rank P = 0.31) and median survivals were 15.2 and 14.9 months, respectively (log-rank P = 0.88). Covariate analysis did not alter these findings. Median leukocyte nadirs were 1800 for CFP and 1500 for CMFP, with 22% and 21%, respectively, having nadirs less than 1000/microliters. Emesis was more frequent on CFP (49%) than on CMFP (26%) but was severe in only 7% and 5%, respectively. It is concluded that despite a higher response rate on CMFP and some differences in toxicities including a higher reported incidence of emesis on CFP, there was no substantial difference in efficacy or tolerability between the two regimens.

Adult↗
PubMed1989

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.

Adult↗
PubMed1989

Results of salvage hormonal therapy and salvage chemotherapy in women failing adjuvant chemotherapy after mastectomy for breast cancer.

We have evaluated the results of salvage systemic therapy in 257 patients with breast cancer recurrent after surgical adjuvant treatment with cyclophosphamide, fluorouracil, and prednisone (CFP) with or without tamoxifen. The overall objective response rate to salvage hormonal therapy was 29% (47 responses in 161 patients) and to salvage chemotherapy was 28% (43 responses in 156 patients). Response rates to salvage chemotherapy were similar whether or not prior salvage hormonal therapy or local modalities had been administered. Retreatment with CFP as a salvage chemotherapy yielded responses in 11 of 44 patients (25%). Response rates were similar for patients who began salvage CFP less than or equal to 12 months or greater than 12 months after completion of adjuvant CFP. We conclude that when this unselected population of patients failing adjuvant CFP is considered, 1) response rates to salvage chemotherapy were low regardless of whether or not prior salvage hormonal or local therapies were given, 2) repeating adjuvant chemotherapy (CFP) following relapse produced a low response rate, and 3) response rates to salvage hormonal therapy were low, but on the order of those observed in patients with advanced disease unselected by estrogen receptor status who are treated with first line hormonal maneuvers.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A prospective, randomized controlled trial of megestrol acetate among high-risk patients with resected malignant melanoma.

In light of some evidence that hormonal factors may impact on malignant melanoma, we performed a randomized trial of megestrol acetate versus observation among 67 patients with high-risk resected stage I or stage II (nodal) malignant melanoma. Following stratification by relevant prognostic factors, we observed a statistical significance in survival advantage for megestrol acetate that approached 7.6 versus 2.6 years, median survival; two-sided log rank p = 0.06. Disease-free survival was also greater for patients who received this hormonal therapy (3.4 versus 1.1 years, median disease-free survival), but the difference was not statistically significant (two-sided log rank p = 0.20). The most noteworthy side effects were weight gain (median 6-month gain of 8.2 kg) and impotence. Fully recognizing the hazards of limited sample analyses and the need for confirmatory trials, our findings suggest a possible role for megestrol acetate as adjuvant therapy for selected patients with malignant melanoma.

Female↗
PubMed1989

Evaluation of menogaril in patients with metastatic sarcomas and no prior chemotherapy exposure.

Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin. To evaluate the possible therapeutic benefit of this drug, we studied menogaril in 21 patients with metastatic sarcomas who had received no prior chemotherapy. Menogaril was administered intravenously over 1 h every 3-4 weeks at a dose of 200 mg/m2 in 500 ml of 5% dextrose in water. One patient experienced a partial regression of pulmonary metastases from malignant fibrous histiocytoma of bone (response rate of 5% with 95% confidence interval of 0.1-23.8%). Two additional patients experienced minor reductions in tumor size. The remaining 18 patients had no improvement from menogaril. The median time to disease progression was 7 weeks in all patients treated. Toxicity was acceptable, consisting primarily of leukopenia with 12 patients (57%) and 19 patients (90%) developing nadir leukocyte counts less than 2000 and 3000/microL, respectively. Cardiac toxicity was not encountered; however, only seven patients received greater than or equal to 3 cycles of menogaril. We conclude that menogaril does not appear to be useful at this dose and schedule in the treatment of metastatic sarcomas despite the use of near maximal doses in patients with no prior chemotherapy exposure.

Adult↗