PubMed Health⌕ Search

Biomedical subjects

Nuhad K Ibrahim

Publications and source records attributed to Nuhad K Ibrahim.

16 recordsLinked to original sources
PubMed2007

Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen.

PURPOSE: Findings from our previously published phase III randomized trial showed a high pathologic complete remission (CR) rate in patients with human epidermal growth factor receptor 2-positive breast cancer after the concurrent administration of trastuzumab and paclitaxel, followed by concurrent trastuzumab and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) preoperative chemotherapy. The safety and efficacy data of initial population were updated, with inclusion of additional experience with the same therapy. STUDY DESIGN: The initial randomized study population of 42 patients were randomly assigned to either four cycles of paclitaxel followed by four cycles of FEC or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. All data were updated through November 2005. RESULTS: Pretreatment characteristics of the initial patients and of the second cohort were similar. In the second cohort, pathologic CR rate was 54.5% (95% confidence interval, 32.2-75.6%) and the pathologic CR rate among all patients treated with chemotherapy plus trastuzumab was 60% (95% confidence interval, 44.3-74.3%). Three patients in the chemotherapy only group have recurred, and one has died. There has been no recurrences in the patients randomized to chemotherapy plus trastuzumab, and the estimated disease-free survival at 1 and 3 years was 100% (P = 0.041). In additional cohort treated with chemotherapy and trastuzumab at the median follow-up of 16.3 months, no patients had recurred. No new safety concerns were observed in this study. CONCLUSION: Our expanded cardiac safety data and the updated efficacy data showed that the natural history of this subset of breast cancer patients can be substantially modified by this treatment approach.

Adult↗
PubMed2006

The impact of immediate breast reconstruction on the technical delivery of postmastectomy radiotherapy.

PURPOSE: To quantify the impact of immediate breast reconstruction on postmastectomy radiation therapy (PMRT) planning. METHODS: A total of 110 patients (112 treatment plans) who had mastectomy with immediate reconstruction followed by radiotherapy were compared with contemporaneous stage-matched patients who had undergone mastectomy without intervening reconstruction. A scoring system was used to assess optimal radiotherapy planning using four parameters: breadth of chest wall coverage, treatment of the ipsilateral internal mammary chain, minimization of lung, and avoidance of heart. An "optimal" plan achieved all objectives or a minor 0.5 point deduction; "moderately" compromised treatment plans had 1.0 or 1.5 point deductions; and "major" compromised plans had > or =2.0 point deductions. RESULTS: Of the 112 PMRT plans scored after reconstruction, 52% had compromises compared with 7% of matched controls (p < 0.0001). Of the compromised plans after reconstruction, 33% were considered to be moderately compromised plans and 19% were major compromised treatment plans. Optimal chest wall coverage, treatment of the ipsilateral internal mammary chain, lung minimization, and heart avoidance was achieved in 79%, 45%, 84%, and 84% of the plans in the group undergoing immediate reconstruction, compared respectively with 100%, 93%, 97%, and 92% of the plans in the control group (p < 0.0001, p < 0.0001, p = 0.0015, and p = 0.1435). In patients with reconstructions, 67% of the "major" compromised radiotherapy plans were left-sided (p < 0.16). CONCLUSIONS: Radiation treatment planning after immediate breast reconstruction was compromised in more than half of the patients (52%), with the largest compromises observed in those with left-sided cancers. For patients with locally advanced breast cancer, the potential for compromised PMRT planning should be considered when deciding between immediate and delayed reconstruction.

Breast Neoplasms↗
PubMed2006

Nanoparticle albumin-bound paclitaxel for treatment of metastatic breast cancer.

Two taxanes, paclitaxel and docetaxel, are among the most widely used chemotherapeutic agents in solid tumor oncology, with efficacy against tumors of the breast, lung, head and neck, ovary, prostate, stomach and urothelium. The taxanes have been studied extensively and have been proven effective for treating early and advanced breast cancer. However, paclitaxel and docetaxel are both highly hydrophobic compounds, requiring synthetic solvents for parenteral administration. The solvents in commercially available preparations cause life-threatening toxic effects and decreased efficacy, and they are inconvenient to administer. Nanoparticle albumin-bound paclitaxel (nabP) is a novel, solvent-free formulation of paclitaxel. With nabP, in contrast to standard paclitaxel, life-threatening hypersensitivity reactions have not been observed, and it can be administered safely without steroid and antihistamine premedication. Furthermore, nabP exploits cellular and tumor transport mechanisms to preferentially target tumor cells. Data from phase III studies of metastatic breast cancer demonstrated higher response rates, longer time to progression and an improved toxicity profile for nabP compared with standard paclitaxel. The U.S. Food and Drug Administration approved nabP in late 2004 for treatment of metastatic breast cancer after failure of an anthracycline-based regimen.

Breast Neoplasms↗
PubMed2006

Aromatase inhibitors in breast cancer: an overview.

We examined published reports on the use of aromatase inhibitors in postmenopausal patients with hormone receptor-positive breast cancer. Our data were obtained through a MEDLINE search of literature published in English. Current data indicate that aromatase inhibitors are equivalent or superior to tamoxifen as first-line therapy for metastatic breast cancer and as neoadjuvant treatment for primary breast cancer. In addition, randomized studies have shown that aromatase inhibitors can be administered instead of tamoxifen as a single agent for 5 years or sequentially with tamoxifen for 5 or 10 years. These choices should be discussed with the patient, considering the estimated risk for recurrence and other associated comorbid conditions such as osteoporosis and thromboembolism.

Antineoplastic Agents↗
PubMed2005

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer.

PURPOSE: ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease. RESULTS: Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions. CONCLUSION: ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.

Adult↗
PubMed2005

Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks.

PURPOSE: To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. RESULTS: A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

Adult↗
PubMed2005

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.

Adult↗
PubMed2004

Colitis in patients with breast carcinoma treated with taxane-based chemotherapy.

BACKGROUND: Colitis is a rare but serious gastrointestinal complication associated with taxane-based chemotherapy in patients with cancer. The incidence, clinical presentation, and outcome of colitis in patients with breast carcinoma treated with taxane-based chemotherapy is not known. METHODS: The authors searched their electronic database and identified patients with breast carcinoma who were treated with taxane-based chemotherapy between January 1997 and December 1999. Patients diagnosed with colitis were identified and their presentation and clinical outcomes were analyzed. RESULTS: During the study period, 1350 patients received taxane-based chemotherapy. Sixty-four patients were admitted to The University of Texas M. D. Anderson Cancer Center (Houston, TX) (73 admissions) for gastrointestinal complications. Neutropenia and/or fever accounted for 56 of these admissions. Fourteen patients (16 admissions) were diagnosed with colitis. All had abdominal pain at median Day 6 of their chemotherapy cycle (range, 3-8 days), with or without other symptoms. Computed tomography scans of the abdomen and pelvis were abnormal for the 10 patients tested, whereas only 3 of the 9 patients who underwent radiographic abdominal series had abnormal findings. Two patients had a colonoscopy that confirmed the diagnosis of colitis. Blood cultures were positive in only 3 (20%) of 15 colitis events. All eight patients tested for Clostridium difficile toxin were negative. One patient died of sepsis. An autopsy subsequently revealed cecal ulceration. Two patients had bowel perforations requiring hemicolectomy. Colitis recurred in two patients after they resumed taxane-based chemotherapy without dose reduction. Dose reductions prevented the recurrence of colitis in seven patients. Treatment discontinuation of taxane-based chemotherapy also prevented disease recurrence. CONCLUSIONS: Acute abdominal pain in patients with breast carcinoma treated with taxane-based chemotherapy signaled a potentially fatal colitis, and warrants aggressive supportive care. Dose reduction or discontinuation of taxane-based chemotherapy may prevent the recurrence of colitis.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Total RNA yield and microarray gene expression profiles from fine-needle aspiration biopsy and core-needle biopsy samples of breast carcinoma.

BACKGROUND: Gene expression profiling should be applicable to needle biopsy samples if microarray technology is to become practically useful for clinical research or management of breast carcinoma. This study compared gene expression profiles derived from fine-needle aspiration biopsy (FNAB) and from core needle biopsy (CBX). METHODS: Total RNA was extracted from single FNAB and CBX samples. Corresponding pairs of FNAB and CBX were analyzed for similarity of gene expression profiles using cDNA microarrays that contain 30721 human sequences. A subset of genes that distinguished CBX samples from FNAB samples was evaluated in a larger group of needle biopsy samples and in a published genomic database derived from 78 sporadic breast carcinomas with known clinical outcome. RESULTS: Sixty-eight patients with newly diagnosed breast carcinoma were included in the current study. Sixty-five patients underwent FNAB (17 had both FNAB and CBX) and 3 underwent CBX only. Extracted RNA was of suitable quality for hybridization in 46 (71%) FNABs and 15 (75%) CBXs. Total RNA yield in those samples was similar for single-pass FNAB (mean = 3.6 microg and median = 2.2 microg; n = 46) and CBX (mean = 2.8 microg and median = 2.0 microg; n = 15), with 1 microg or more of total RNA in all cases. Transcriptional profiling was performed successfully in all cases when it was attempted, in a total of 50 samples (38 FNABs and 12 CBXs), including matched FNAB and CBX samples from 10 patients. There were differences in gene expression profiles in 10 matched FNAB and CBX sample pairs. Genes that were expressed differently in CBX samples, compared with FNAB samples, were recognized as being predominantly from the endothelium, fibroblasts, myofibroblasts or smooth muscle, and histiocytes. Corresponding microscopic cell counts from FNABs demonstrated means of 80% tumor cells, 15% lymphocytes, and 5% stromal cells, whereas CBXs contained 50% tumor cells, 20% lymphocytes, and 30% stromal cells. Considering that CBXs are approximately six-fold richer in nonlymphoid stromal cells than FNABs and that CBXs differentially express a set of recognized stromal genes, the authors used these biopsies to define a transcriptional profile of breast carcinoma stroma. A set of 120 genes differentially expressed in CBXs was assessed independently in a published breast carcinoma genomic database to classify breast carcinomas based on stromal gene expression. Subgroups of tumors with low or high stromal signal were identified, but there was no correlation with the development of systemic metastases within 5 years. CONCLUSIONS: Both FNAB and CBX yield a similar quality and quantity of total RNA and are suitable for cDNA microarray analyses in approximately 70-75% of single-pass samples. Transcriptional profiles from FNAB and CBX of the same tumor generally are similar and are driven by the tumor cell population. The authors concluded that each technique has relative advantages. The FNABs provide transcriptional profiles that are a purer representation of the tumor cell population, whereas transcriptional profiles from CBXs include more representation from nonlymphoid stromal elements. Selection of the preferred needle biopsy sampling technique for genomic studies of breast carcinomas should depend on whether variable stromal gene expression is desirable in the samples.

Adult↗
PubMed2003

Clinical development of the STn-KLH vaccine (Theratope).

The development of active specific immunotherapy depends on the identification of altered cancer cell-specific molecules or epitopes that are immunogenic. Many cancer-specific peptide or glycoprotein target antigens have been identified. Tumors carrying aberrant epitopes as a result of underglycosylation of mucins are associated with poor prognosis in many epithelial cancers. The aberrant mucin sialyl-Tn (STn) epitope, in addition to being a predictor of poor prognosis when expressed in tumors, is associated with increased aggressiveness and metastatic potential, making it a promising target for immunotherapy. The STn-keyhole limpet hemocyanin (KLH) vaccine (Theratope) is an investigational active specific immunotherapy consisting of a synthetic STn epitope conjugated to a high molecular weight protein carrier, KLH. The immune response generated by the STn-KLH vaccine is both humoral and cellular. More than 1000 breast cancer patients with metastatic disease are currently enrolled in a phase III clinical trial to assess the safety and efficacy of the STn-KLH vaccine. Interim analysis from a current phase III trial has confirmed the safety of the STn-KLH vaccine, and the clinical outcome awaits the final analysis expected in 2003.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2002

Phase I study of vinorelbine and docetaxel with granulocyte colony-stimulating factor support in the treatment of metastatic breast cancer.

PURPOSE: Vinorelbine and docetaxel are two active agents in the treatment of metastatic breast cancer. When given together, these drugs exhibit synergistic antitumor activity without significant pharmacokinetic interaction. The dose-limiting toxicities of this combination are neutropenic fever and mucositis. Adding granulocyte colony-stimulating factor (G-CSF) might lessen the toxicity and increase the maximum tolerated dose (MTD) of this combination. The aim of this study was to determine the MTD of vinorelbine and docetaxel given in combination with G-CSF. PATIENTS AND METHODS: Between August 1997 and December 1998, 14 patients with metastatic breast cancer were enrolled in this study. All patients had received doxorubicin-based therapy, and 46% had received paclitaxel in the adjuvant or neoadjuvant setting. Patients were treated with vinorelbine at a starting dose of 20 mg/m2 intravenously over 10 min on days 1 and 5 and docetaxel at a starting dose of 85 mg/m2 intravenously over 1 hr on day 1, following the vinorelbine. Treatments were repeated every 21 days. Prophylactic G-CSF 5 mcg/kg was given subcutaneously on days 3-10. Toxicity was graded according to the National Cancer Institute's grading system. RESULTS: A total of 65 cycles was administered at dose levels 0, -1, -2, and -3. The median absolute granulocyte count nadir for all courses was 200 mm(-3) (range, 0.1-7700 mm(-3)), and the median time to this nadir was 9 days (range, 7-30). The median platelet nadir was 163 (range, 27-401 k), and the median time to this nadir was 8 days (range, 7-30). The most common grade 3 nonhematologic toxicities for all courses were fatigue and myalgia, which occurred in 32 and 10 cycles, respectively. Neutropenic fever was encountered in 11 cycles. Three patients developed colitis-like pictures, two of whom died as a result. Consequently, the protocol was closed to accrual before a MTD was reached. CONCLUSION: The combination of vinorelbine, docetaxel, and G-CSF in our hands has proven to be a toxic regimen, even when relatively low doses of vinorelbine and docetaxel are given. Meticulous observation of patients receiving this combination is warranted since the combination resulted in two deaths in this study.

Adult↗
PubMed2002

Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel.

PURPOSE: ABI-007 is a novel Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. The absence of Cremophor EL may permit ABI-007 to be administered without the premedications used routinely for the prevention of hypersensitivity reactions. Furthermore, this novel formulation permits a higher paclitaxel concentration in solution and, thus, a decreased infusion volume and time. This Phase I study examines the toxicity profile, maximum tolerated dose (MTD), and pharmacokinetics of ABI-007. EXPERIMENTAL DESIGN: ABI-007 was administered in the outpatient setting, as a 30-min infusion without premedications. Doses of ABI-007 ranged from 135 (level 0) to 375 mg/m2 (level 3). Sixteen patients participated in pharmacokinetic studies. RESULTS: Nineteen patients were treated. No acute hypersensitivity reactions were observed during the infusion period. Hematological toxicity was mild and not cumulative. Dose-limiting toxicity, which occurred in 3 of 6 patients treated at level 3 (375 mg/m2), consisted of sensory neuropathy (3 patients), stomatitis (2 patients), and superficial keratopathy (2 patients). The MTD was thus determined to be 300 mg/m2 (level 2). Pharmacokinetic analyses revealed paclitaxel C(max) and area under the curve(inf) values to increase linearly over the ABI-007 dose range of 135-300 mg/m2. C(max) and area under the curve(inf) values for individual patients correlated well with toxicity. CONCLUSIONS: ABI-007 offers several features of clinical interest, including rapid infusion rate, absence of requirement for premedication, and a high paclitaxel MTD. Our results provide support for Phase II trials to determine the antitumor activity of this drug.

Adult↗
PubMed2002

Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial.

PURPOSE: Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy. In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer. EXPERIMENTAL DESIGN: Five hundred twenty-four patients were randomized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8 cycles of FAC alone. Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting. Planned duration of therapy was the same in all patients. After completion of 8 cycles of chemotherapy, those patients who were > or =50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years. RESULTS: Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5-89 months. Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups was not statistically significant (P = 0.09). The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66. CONCLUSION: Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence; however, differences were not statistically significant. At the time of this analysis, there have been 47 deaths. The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality.

Antineoplastic Agents, Phytogenic↗
PubMed2002

A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer.

PURPOSE: This Phase II study was designed to determine the efficacy and toxicity of combination doxorubicin and paclitaxel as front-line treatment for metastatic breast cancer. EXPERIMENTAL DESIGN: Eligible patients had no prior anthracycline or taxane therapy and normal cardiac function. They were treated with bolus doxorubicin 60 mg/m2, followed by paclitaxel 200 mg/m2, as either 1- or 3-h infusions for six to seven cycles. Single-agent paclitaxel was continued thereafter. Serial multiple gated acquisition scans were performed, and endomyocardial biopsies were performed for consenting patients. RESULTS: Eighty-two patients were enrolled with a median age of 53 years (range, 32-78 years). Of 79 evaluable patients, 58.2% had an objective response (3.8% complete response + 54.4% partial response), 34.2% had stable disease, and 7.6% had progressive disease. With median follow-up of 37.5 months, median time to progression was 7 months; median survival was 31 months. Multiple gated acquisition scans were performed in 82 of 82 patients at baseline, 75 of 82 patients at a total doxorubicin dose of 60-180 mg/m2, 62 of 68 patients at 200-300 mg/m2, 18 of 52 patients at 310-360 mg/m2, and 4 of 8 patients at 420 mg/m2. Median ejection fractions were 62.5, 60, 57.5, 52.5, and 32%, respectively. Fifteen of 82 (18.3%) patients had a decrease in ejection fraction > or = 15% to an absolute ejection fraction < or = 50%. Eight of these 15 patients (53%) developed clinical congestive heart failure: 4 of 8 (50%) who received a total doxorubicin dose of 420 mg/m2 versus 4 of 74 (5.4%) who received a dose < or = 360 mg/m2 (P = 0.002). CONCLUSIONS: When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.

Adult↗
PubMed2002

Toxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer.

To determine the toxicity and immunogenicity of the HER-2/neu, HLA-A2-restricted peptide E75 in patients with metastatic breast and ovarian cancer, 14 patients were vaccinated with escalating amounts of E75 (100, 500, and 1000 microg) mixed with 250 microg granulocyte macrophage colony-stimulating factor as adjuvant. Each vaccine dose was administered in a total volume of 1.5 ml divided into four intradermal injections and administered weekly for 4 weeks, followed by monthly boosts for a total of 10 injections. Vaccinations were well tolerated without significant toxicity. Blood was drawn before, at 8 weeks, and up to 13-16 months after vaccination for measurement of cellular immunity. Seven of 8 patients tested had significant delayed type hypersensitivity to E75 defined as >5 mm induration. Peripheral blood mononuclear cells from 5 of 9 patients tested proliferated to E75 with a stimulation index of > or = 2.0. Of 8 vaccinated patients tested for induction of a CTL response, 4 responded to stimulation by autologous dendritic cells plus cytokines by eliciting E75-specific lytic activity consistent with the presence of activated/memory cells, 2 others after in vitro stimulation with E75 + interleukin-12 +/- anti-CD152(33KD), whereas 2 others did not respond. Four patients with E75-specific CTLs present specifically recognized E75 on indicator tumors as demonstrated by cold-target inhibition of tumor lysis. These 4 patients showed E75-specific IFN-gamma production. peripheral blood mononuclear cell from 3 of these patients proliferated to E75, but stimulation indices were higher in the prevaccine samples. All 4 of the patients showed DTH responses to E75. These results demonstrate that vaccination with E75+ granulocyte macrophage colony-stimulating factor can induce both peptide-specific IFN-gamma and epitope specific CTLs, which lyse HER-2/neu+ tumors in stage IV patients.

Abatacept↗