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Biomedical subjects

James N Ingle

Publications and source records attributed to James N Ingle.

At least 37 records · Page 2Linked to original sources
PubMed2005

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.

BACKGROUND: We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. METHODS: The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel. RESULTS: By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831. CONCLUSIONS: Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)

Adult↗
PubMed2005

Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women.

PURPOSE: To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. METHODS: Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. RESULTS: Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). CONCLUSION: Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.

Administration, Oral↗
PubMed2005

Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17.

BACKGROUND: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. METHODS: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. RESULTS: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P < .001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. CONCLUSION: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients.

Aged↗
PubMed2005

A phase II trial of docetaxel and carboplatin as first-line chemotherapy for metastatic breast cancer: NCCTG study N9932.

OBJECTIVE: A phase II multi-institutional clinical trial conducted to evaluate the efficacy and tolerability of docetaxel and carboplatin as first-line therapy for women with metastatic breast cancer. METHODS: Patients had histologically confirmed metastatic breast cancer with at least one measurable lesion. Prior adjuvant chemotherapy was permitted, provided that at least 12 months had elapsed between any prior taxane and platinum therapy. Patients received docetaxel 75 mg/m(2) with carboplatin AUC 6 mg/ml.min every 21 days until disease progression or prohibitive toxicity. RESULTS: All 53 patients enrolled were evaluable for response and toxicity. Median number of cycles delivered was 6. Overall response rate was 60%, with 3 complete responses (6%) and 29 partial responses (54%). Median time to disease progression was 9.6 months. Median survival time was 20.4 months. Myelosuppression was the predominant toxicity, with grade 3 or 4 neutropenia occurring in 94% of patients and 15% of patients experiencing febrile neutropenia. The overall incidence (grades 1-3) of neurosensory toxicity was 57% and neuromotor toxicity was 25%, respectively, with grade 3 toxicity occurring in 4% of patients each. CONCLUSIONS: The combination of docetaxel and carboplatin is highly active in metastatic breast cancer. Prophylactic growth factor support is recommended in any further evaluation of this combination in the treatment of patients with breast cancer.

Adult↗
PubMed2005

Evaluation of a panel of tumor markers for molecular detection of circulating cancer cells in women with suspected breast cancer.

PURPOSE: We examined the feasibility of using molecular characterization of circulating tumor cells as a method for early detection of breast cancer. RESEARCH DESIGN: Women without a prior history of cancer who had a breast abnormality detected on imaging followed by a breast biopsy were enrolled in this study. Density gradient centrifugation and immunomagnetic capture were used to enrich for epithelial cells from approximately 20 mL of blood. Real-time reverse transcription-PCR was used to quantitate the expression levels of the highly breast-specific genes, mammaglobin, gamma-aminobutyric acid type A receptor pi subunit (GABA A(pi)), B305D-C, and B726P in the epithelial cell-enriched samples. RESULTS: The assay was technically feasible in 154 of 199 accrued patients. From their clinical assessment, 100 patients had benign breast disease, 10 patients had ductal carcinoma in situ, and 44 patients had invasive breast cancer. We constructed a diagnostic test that classified patients with mammaglobin levels of at least 32.2 copies/pg beta-actin (units) in their circulating epithelial cells as positive for invasive breast cancer. This resulted in a sensitivity and specificity of 63.3% and 75.0%, respectively. A diagnostic test that classified patients as positive for invasive breast cancer when either mammaglobin levels were >46.3 units or B305D-C levels were >11.6 units increased the sensitivity and specificity to 70.5% and 81.0%, respectively. In the latter test, 12 of the 14 node-positive breast cancer patients were correctly identified. Including GABA A(pi) and B726P in the test did not increase its diagnostic potential. CONCLUSIONS: These results suggest that molecular characterization of circulating epithelial cells using mammaglobin and B305D-C offers potential for early detection of invasive breast cancer.

Adult↗
PubMed2005

Serum soluble epidermal growth factor receptor concentrations decrease in postmenopausal metastatic breast cancer patients treated with letrozole.

Previous studies have implicated estrogen as a regulator of epidermal growth factor receptor (EGFR) expression in breast tumors. We therefore speculated that estrogen might modulate serologic soluble EGFR (sEGFR) concentrations in breast cancer patients. Accordingly, we measured serum sEGFR concentrations in postmenopausal women with metastatic breast cancer (MBC) treated with letrozole, an aromatase inhibitor that blocks estrogen synthesis. Serum specimens were obtained prior to and following 1 and 3 months of letrozole therapy. We report that sEGFR concentrations do not differ between MBC patients prior to letrozole treatment and age- and postmenopause-matched healthy women (P = 0.468). In contrast, however, sEGFR concentrations decreased significantly in 76% of MBC patients after both 1 month (P = 0.006) and 3 months (P = 0.003) of letrozole therapy versus pretreatment concentrations. Within the limitations of this study, we found no evidence for an association between pretreatment sEGFR concentrations or decreased treatment sEGFR concentrations and either progression-free or overall survival. Nonetheless, we conclude that future prospective studies are warranted to determine if baseline and/or longitudinal serum sEGFR concentrations may be useful for predicting disease progression and survival, and/or for monitoring responsiveness to aromatase inhibitors or other endocrine therapies in breast cancer patients.

Antineoplastic Agents↗
PubMed2005

Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings.

The recent past has witnessed the appearance of substantial data relating to endocrine therapy of breast cancer. In the adjuvant therapy setting in early breast cancer, several large, well-conducted, randomized, double-blind clinical trials have provided evidence for the value of the third-generation aromatase inhibitors (AI) anastrozole, exemestane, and letrozole. The three major studies to date [i.e., Arimidex, tamoxifen alone, or in combination (ATAC), International Exemestane Study (IES), and letrozole after 5 years of tamoxifen (MA.17)] evaluated three different populations of women from the standpoints of duration of prior tamoxifen and thus time since the treatment of the primary breast cancer. A consistent pattern of improvement in disease-free survival was seen whether the control arm was tamoxifen (ATAC and IES) or placebo following tamoxifen (MA.17). From a toxicity standpoint, the major findings with the AIs were a decreased incidence of thromboembolic events and endometrial cancers but an increase in musculoskeletal complaints and potential for decreasing bone density. The last issue should be clarified with ongoing studies addressing the impact of the three AIs on bone density and fractures. In summary, based on ATAC, IES, and MA.17, respectively, the following conclusions can be drawn relating to postmenopausal women with hormone receptor positive early breast cancer: anastrozole is a reasonable choice for initial endocrine adjuvant therapy, exemestane should be considered for women who have received 2 to 3 years of tamoxifen, and letrozole should be considered for those who have completed about 5 years of tamoxifen. In the prevention setting, tamoxifen has been evaluated in multiple trials involving >28,000 women and, despite clear evidence of benefit, the level of acceptance of this agent by women seems to be low. Two recently developed prevention trials, IBIS 2 and MAP.3, involve the study of aromatase inhibitors against a placebo control rather than tamoxifen. Whereas the recent adjuvant trials have established the value of the third-generation aromatase inhibitors in early-stage breast cancer, the marked reductions in contralateral breast cancers seen in these trials suggest they will be of value in the prevention setting in women at increased risk of developing the disease.

Antineoplastic Agents↗
PubMed2005

Aromatase inhibitors for therapy of advanced breast cancer.

In postmenopausal women with advanced breast cancer, numerous phase III trials have been performed comparing the third-generation non-steroidal aromatase inhibitors (NS-AIs) anastrozole and letrozole and the steroidal AI (S-AI) exemestane in the "first-line" setting against tamoxifen and in the "second-line" setting against megestrol acetate. In both settings, the AIs were at least as efficacious or superior in some endpoints with a preferable toxicity profile including a lower incidence of thrombotic events. Relatively small differences in potency between the three AIs have been identified and it has not been demonstrated that these differences have clinical implications. The recent establishment of the value of AIs in the adjuvant setting for postmenopausal women will impact on their utilization in advanced disease. In premenopausal women the third-generation AIs have not been studied as monotherapy and there is a paucity of data in combination with ovarian function suppression in the advanced disease setting. The main area of future investigations for the AIs in premenopausal women will be in the adjuvant therapy setting in combination with suppression of ovarian function.

Anastrozole↗
PubMed2005

Phase II study of gemcitabine plus cisplatin in patients with metastatic breast cancer: a North Central Cancer Treatment Group Trial.

BACKGROUND: This 2-stage, phase II cooperative group trial examined the efficacy and toxicity of 1000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin weekly for 3 weeks and repeated every 28 days for patients with previously treated metastatic breast cancer. METHODS: Eligible patients had to have measurable metastatic disease. Progression on prior treatment with at least 1 chemotherapy program for metastatic disease and 1 prior anthracycline and/or taxane-containing regimen in either the metastatic or adjuvant setting was required. Patients who had received more than 2 chemotherapy treatments were not eligible for this study. RESULTS: Fifty-eight eligible patients were entered on this 2-stage study. A 38% incidence of grade 4 thrombocytopenia observed in the first stage of accrual required lowering the chemotherapy doses to 800 mg/m2 gemcitabine plus 20 mg/m2 cisplatin weekly for the first 3 weeks of a 4-week cycle during the second stage of the study. The overall response rate was 29% (95% confidence interval [CI], 11-52%) among patients receiving the original study dose and 32% (95% CI, 18-50%) for patients receiving the lower dose. In the original- and lower-dose groups, median time to progression was 30.7 weeks (95% CI, 12.7-43.4 weeks) and 26.0 weeks (95% CI, 19.0-32.1 week), respectively. Median survival of the original- and low-dose groups was 67.9 weeks (95% CI, 42.3-90.6 weeks) and 54.1 weeks (95% CI, 41.6-73.6 weeks), respectively. Hematologic toxicities were more manageable in the lower-dose group, whereas the nonhematologic toxicity profile was similar in the 2 dose groups. CONCLUSIONS: The response rate of this combination of gemcitabine and cisplatin is similar to that reported by other investigators but may not differ substantially from reports with single-agent gemcitabine in this patient population. The original dose level we used had unacceptable toxicity, which required lowering the doses of both gemcitabine and cisplatin by 20% to achieve acceptable toxicity and preserve clinical activity.

Adult↗
PubMed2005

Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252.

PURPOSE: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial. PATIENTS AND METHODS: Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m(2) dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m(2) dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity. HER2 status was confirmed by a central laboratory review. RESULTS: The overall response rate (ORR) with every-3-week therapy was 65% (90% confidence interval [CI], 51%-77%), with a median time to disease progression of 9.9 months and median overall survival (OS) time of 2.3 years. The ORR with weekly therapy was 81% (90% CI, 70%-90%), with a median time to disease progression of 13.8 months and a median OS time of 3.2 years. Hematologic and nonhematologic toxicities occurred significantly less frequently with weekly therapy versus every-3-week therapy: grade 3/4 neutropenia (52% vs. 88%); grade 3 thrombocytopenia (4% vs. 30%); and grade 3 neurosensory toxicity (2% vs. 19%), respectively. CONCLUSIONS: Every-3-week and weekly regimens of paclitaxel/carboplatin/trastuzumab are highly active in women with HER2-overexpressing MBC. However, fewer patients developed severe neutropenia, leukopenia, or thrombocytopenia with the weekly schedule.

Adult↗
PubMed2004

Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196.

PURPOSE: To determine whether a matrix metalloproteinase inhibitor improves progression-free survival (PFS) in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy. PATIENTS AND METHODS: One hundred seventy-nine eligible patients were randomly assigned to receive oral marimastat (10 mg bid; n = 114) or a placebo (n = 65) within 3 to 6 weeks of completing six to eight cycles of first-line doxorubicin- and/or taxane-containing chemotherapy for metastatic disease. Patients were evaluated every 3 months until disease progression. RESULTS: When comparing placebo with marimastat, there was no significant difference in PFS (median, 3.1 months v 4.7 months, respectively; hazard ratio, 1.26; 95% CI, 0.91 to 1.74; P = .16) or overall survival (median, 26.6 months v 24.7 months, respectively; hazard ratio, 1.03; 95% CI, 0.73 to 1.46; P = .86). Patients treated with marimastat were more likely to develop grade 2 or 3 musculoskeletal toxicity (MST), a known complication of the drug indicative of achieving a biologic effect, compared with patients administered placebo (63% v 22%, respectively; P < .0001). Patients with grade 2 or 3 MST had significantly inferior survival compared with patients who had grade 0 or 1 MST (median, 22.5 months v 28.2 months; P = .04). In addition, patients who had a marimastat plasma concentration of at least 10 ng/mL at month 1 and/or 3 were significantly more likely to have grade 2 to 3 MST (P < .0001). CONCLUSION: Marimastat does not prolong PFS when used after first-line chemotherapy for metastatic breast cancer. Patients with higher marimastat levels exhibited MST, and MST was associated with inferior survival.

Administration, Oral↗
PubMed2004

American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004.

PURPOSE: To update the 2003 American Society of Clinical Oncology technology assessment on adjuvant use of aromatase inhibitors. RECOMMENDATIONS: Based on results from multiple large randomized trials, adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence. Neither the optimal timing nor duration of aromatase inhibitor therapy is established. Aromatase inhibitors are appropriate as initial treatment for women with contraindications to tamoxifen. For all other postmenopausal women, treatment options include 5 years of aromatase inhibitors treatment or sequential therapy consisting of tamoxifen (for either 2 to 3 years or 5 years) followed by aromatase inhibitors for 2 to 3, or 5 years. Patients intolerant of aromatase inhibitors should receive tamoxifen. There are no data on the use of tamoxifen after an aromatase inhibitor in the adjuvant setting. Women with hormone receptor-negative tumors should not receive adjuvant endocrine therapy. The role of other biomarkers such as progesterone receptor and HER2 status in selecting optimal endocrine therapy remains controversial. Aromatase inhibitors are contraindicated in premenopausal women; there are limited data concerning their role in women with treatment-related amenorrhea. The side effect profiles of tamoxifen and aromatase inhibitors differ. The late consequences of aromatase inhibitor therapy, including osteoporosis, are not well characterized. CONCLUSION: The Panel believes that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen. Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options.

Aged↗
PubMed2004

Effects of exemestane and tamoxifen in a postmenopausal breast cancer model.

PURPOSE: To optimize treatment strategies for postmenopausal breast cancer patients, we investigated the efficacy of the steroidal aromatase inhibitor exemestane alone or in combination with the antiestrogen tamoxifen in a xenograft model of postmenopausal breast cancer. We also determined the effects of these agents in sequential second-line therapy and the effect of the nonsteroidal aromatase inhibitor letrozole on tumors that progressed on the above treatments. EXPERIMENTAL: Aromatase-transfected human estrogen receptor-positive breast cancer cells (MCF-7Ca) were grown as tumors in ovariectomized athymic mice. Animals received subcutaneous injection with vehicle, tamoxifen, exemestane, tamoxifen plus exemestane, and letrozole. Tumor volumes were measured weekly. RESULTS: All treatments were effective initially in suppressing tumor growth as first-line therapy compared with vehicle treatment. Exemestane suppressed tumor growth to a greater extent than tamoxifen. However, the combination of tamoxifen plus exemestane was more effective than either drug alone. After tumor volumes doubled on initial treatment, the mice were crossed over to receive exemestane or tamoxifen. Tumor growth slowed briefly in mice treated with tamoxifen and crossed over to exemestane, but tumor growth continued unabated in those changed from exemestane to tamoxifen. However, letrozole was effective in both groups as third-line therapy for a limited period. Letrozole as initial single agent was the best overall treatment in terms of the degree of tumor suppression and the length of effectiveness of treatment. CONCLUSION: Exemestane was more effective in controlling tumor growth than tamoxifen. In addition, the combination of exemestane plus tamoxifen was clearly more effective than sequential use of these agents in the tumor model. However, the nonsteroidal aromatase inhibitor letrozole as first-line therapy was overall the most effective treatment in controlling tumor growth.

Androstadienes↗
PubMed2004

Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.

PURPOSE: To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2-positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. PATIENTS AND METHODS: Patients were randomly assigned to receive standard doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC. RESULTS: Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had < or = 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had < or = 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients. CONCLUSION: Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.

Adolescent↗
PubMed2004

Efficacy of radiotherapy for ovarian ablation: results of a breast intergroup study.

BACKGROUND: In 1994, the Eastern Cooperative Oncology Group (ECOG) initiated for the Breast Intergroup a randomized clinical trial (E3193) in premenopausal patients with early-stage breast carcinoma (lymph node-negative and receptor-positive, with tumors measuring < or = 3 cm) comparing tamoxifen as adjuvant systemic therapy with tamoxifen and ovarian ablation by one of three different methods. Ovarian ablation could be accomplished either via radiotherapy (RT) (20 Gray [Gy]/10 fractions to a modified pelvic volume), surgical oophorectomy, or goserelin/leuprolide injections as per patient/physician choice. In the current study, we report the efficacy of pelvic RT with this dose-fractionation scheme in the induction of ovarian ablation. METHODS: Twenty-two of 174 patients (13%) who were randomized to treatment with tamoxifen and ovarian ablation received RT for ovarian ablation. RT quality assurance was performed. Of the 22 patients, 19 were treated per protocol, 1 patient had a minor violation (20 elapsed days for 10 RT fractions), and 2 patients had major violations (1 patient who was treated with RT as per protocol but who was treated at a non-Intergroup center, and 1 patient who was treated at a dose of 15 Gy/5 fractions). RESULTS: No acute Grade 3 or 4 (according to the Common Toxicity Criteria of the National Cancer Institute) toxicities were reported during RT. Of the 22 patients receiving RT, evaluable follow-up data were available for 20 patients. Based on postmenopausal levels of estradiol or follicle-stimulating hormone at varying intervals after the completion of RT, 15 of 20 patients (75%) achieved successful ovarian ablation with RT. At a median follow-up of 54 months (range, 21-66 months), no Grade 3 or 4 complications from RT were observed. CONCLUSIONS: Ovarian ablation by RT as performed in the current trial (given at a dose of 20 Gy in 10 fractions to a modified pelvic treatment volume) was found to be effective for ovarian ablation in the majority of patients, but may take some months to be complete. Consequently, patients should be evaluated to ascertain that ablation has been accomplished.

Adult↗
PubMed2004

Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both.

PURPOSE: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. PATIENTS AND METHODS: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks. RESULTS: The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. CONCLUSION: Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.

Adult↗