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G Hortobagyi

Publications and source records attributed to G Hortobagyi.

At least 19 recordsLinked to original sources
PubMed2005

Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer Center and a review of capecitabine toxicity in the literature.

BACKGROUND: Capecitabine is active against anthracycline- and taxane-pretreated metastatic breast cancer. Post-marketing use of capecitabine at the FDA-approved dose (2500 mg/m2/day) leads to unacceptable toxicity in many patients. Dose reductions anecdotally improve tolerability without compromising efficacy. This retrospective analysis was designed to verify these anecdotal reports. PATIENTS AND METHODS: We retrospectively reviewed the records of 141 consecutive patients with metastatic breast cancer identified from pharmacy records as receiving capecitabine outside of a clinical trial between May 1998 and February 1999. Responses were defined as clinical improvement (ID), stabilization of disease (SD) for 6 weeks or longer, or progression (PD). Patients were grouped according to the starting dose level of capecitabine: A=2500+/-5% (dose range 2385-2560) mg/m2/day; B=2250+/-5% (range 2130-2350) mg/m2/day; C < or = 2000+5% (range 1000-2100) mg/m2/day. We also reviewed the safety profile of capecitabine at these doses and performed a safety review of capecitabine in phase II and III metastatic breast and colorectal cancer trials. RESULTS: Clinical data were available for 113 patients (105 for response, 106 for toxicity). The median age was 52.5 years and the mean number of prior metastatic chemotherapy regimens was 2 (range 0-7). The mean capecitabine starting dose was 2220 mg/m2/day and the median number of cycles administered was 4 (range 1-19). The mean tolerated dose was 2040 mg/m2/day (range 960-2670). Grade 3/4 toxic effects at dose levels A, B and C, respectively, included palmar-plantar erythrodysesthesia (33%, 63%, 20%), diarrhea (13%, 12%, 3%), stomatitis (8%, 0%, 3%), and nausea/vomiting (4%, 6%, 5%). Forty per cent of all patients required capecitabine dose reductions; fewer patients treated with 2000 mg/m2/day required dose modification (28%). Five per cent of the patients required discontinuation of capecitabine owing to toxicity. Patients started at the lowest doses of capecitabine did not have poorer response rates or shorter time to progression. CONCLUSIONS: This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.

Adult↗
PubMed2002

Canalicular stenosis secondary to weekly docetaxel: a potentially preventable side effect.

BACKGROUND: The purpose of this study was to describe canalicular stenosis as a mechanism for epiphora (excessive tearing) secondary to weekly docetaxel. PATIENTS AND METHODS: Fourteen patients with metastatic breast cancer who developed epiphora during weekly docetaxel therapy underwent an ophthalmologic examination, and probing and irrigation of the nasolacrimal ducts. The total duration of docetaxel therapy, the duration of treatment at the time of onset of epiphora, the number of infusions, the cumulative dose of docetaxel and the severity of canalicular stenosis were recorded. RESULTS: All 14 patients had anatomic narrowing of the canaliculi as the underlying mechanism for epiphora. Bicanalicular silicone intubation or dacryocystorhinostomy (DCR) was recommended for all 14 patients. Eleven patients underwent surgery and experienced resolution of their symptoms. The three patients who declined surgery continue to have epiphora at the time of this report. CONCLUSIONS: Canalicular stenosis is an underlying mechanism for epiphora in patients receiving weekly docetaxel. Bicanalicular silicone intubation should be considered early in the course of weekly docetaxel therapy to prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, DCR with a permanent pyrex glass tube placement may become necessary to overcome the blockage of tear outflow.

Adult↗
PubMed2001

Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.

PURPOSE: Bisphosphonate therapy has decreased the risk of skeletal complications associated with osteolytic bone lesions in patients with breast cancer and multiple myeloma. The large prospective studies have used 21 to 24 months of treatment. We studied the safety and efficacy of bisphosphonates in a subset of patients who received therapy for more than 24 months. PATIENTS AND METHODS: Patients who received bisphosphonates (pamidronate or zoledronic acid) were identified. Data on skeletal events and laboratory parameters were gathered by chart review. RESULTS: We studied 22 patients who received intravenous pamidronate or zoledronic acid for a duration of 3.6 years (range, 2.2 to 6.0 years). Prolonged therapy was well tolerated. No significant calcium, phosphorus, electrolyte, or WBC count abnormalities were encountered. There was a clinically insignificant decrease in hemoglobin and platelet count and an increase in creatinine in these patients. The fracture rate beyond 2 years was no greater than during the first 2 years of treatment. There were no stress fractures of long bones with prolonged therapy. CONCLUSION: Prolonged treatment with the potent bisphosphonates pamidronate and zoledronic acid seems to be well tolerated and should be studied in prospective, randomized studies to document prolonged skeletal efficacy.

Bone Neoplasms↗
PubMed2000

Oral bisphosphonates: A review of clinical use in patients with bone metastases.

BACKGROUND: This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients. METHODS: Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology. RESULTS: Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases. Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone. CONCLUSIONS: Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis.

Alendronate↗
PubMed2000

Delphi-panel analysis of appropriateness of high-dose chemotherapy and blood cell or bone marrow autotransplants in women with breast cancer.

BACKGROUND: There is controversy whether high-dose chemotherapy and a blood cell or bone marrow autotransplant is a better treatment than conventional-dose chemotherapy for women with local/regional or metastatic breast cancer. Subject selection and time-to-treatment biases make definitive comparison impossible. Recent results of randomized trials are contradictory. OBJECTIVE: Determine appropriateness of high-dose chemotherapy and a blood cell or bone marrow autotransplant in women with breast cancer. PANELISTS: Nine breast cancer experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of 'breast cancer' and 'chemotherapy' and/or 'blood cell' or 'bone marrow transplants'. PROCESS: We used a modified Delphi-panel group judgement process. Clinical variables were permuted to define 2058 clinical settings. Each panelist rated appropriateness of high-dose therapy and an autotransplant versus conventional therapy on a 9-point ordinal scale (1: most inappropriate, 9: most appropriate). An appropriateness index was developed based on median rating and amount of disagreement. The relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. CONCLUSIONS: In women with local/regional breast cancer autotransplants were rated: 1) appropriate in those with > or = 10 cancer-involved lymph nodes; 2) uncertain in those with 4-9 cancer-involved nodes; and 3) inappropriate in women with < or = 3 cancer-involved lymph nodes. In women with metastatic breast cancer autotransplants were rated: 1) appropriate in those with metastases to 'favorable' sites (skin, lymph node, pleura) and a complete or partial response to chemotherapy; 2) uncertain in women with metastases to 'unfavorable' sites (lung, liver, or central nervous system) and a complete response to chemotherapy or those with bone metastases and a complete or partial response or stable disease after chemotherapy; and 3) inappropriate in other settings.

Antineoplastic Agents↗
PubMed2000

A unified definition of clinical anthracycline resistance breast cancer.

The purpose of the study was to determine the response rates (RR) and duration to second- and third-line chemotherapy programmes in patients with anthracycline-resistant breast cancer, utilizing various definitions of anthracycline resistance. This was a retrospective analysis performed on 1335 patients with metastatic breast cancer who participated in consecutive clinical trials of first line, anthracycline-containing combination chemotherapy (ACCC) at the University of Texas MD Anderson Cancer Center between July 1973 and April 1980. Anthracycline-resistant groups were identified using definitions of anthracycline resistance found in the literature: progressive disease as best response to ACCC (Group 1, n = 56 patients); progressive disease while receiving ACCC after an intervening response to the drug (Group 2, n = 84); progressive disease within 6 months of last dose of ACCC (Group 3, n = 233); and progressive disease within 12 months of last dose of ACCC (Group 4, n = 272). Second- and third-line therapies administered to these patients included methotrexate, doxorubicin, mitoxantrone, bisantrene, vinblastine, vindesine, melphalan, mitomycin, cisplatin, etoposide and others, but not taxanes. The distribution of patients' characteristics was similar between the four groups, as was the use of second- and third-line regimens. Response rate (RR) to second-line chemotherapy were 5% and 7.7% for Group 1 and Group 2 respectively. In contrast, RR to second-line chemotherapy were 21.6% and 15% for Group 3 and 4. The differences in response rate between the combination of Groups 1 and 2 and Groups 3 or 4 were significant (P = 0.005 and P = 0.04 respectively). These results indicate that strictly defined anthracycline resistance as defined in Groups 1 and 2 is associated with resistance to many other cytotoxic drugs. The definitions used in Groups 3 and 4 include many patients with responsive tumours, and a more favourable prognosis.

Adult↗
PubMed2000

Adjuvant therapy for breast cancer.

Substantial progress has been made in the diagnosis and management of primary breast cancer over the past three decades. As a result, mortality related to this disease has been decreasing gradually for several years, treatment has become more effective, and side effects and complications related to treatment have decreased. In this report, we review the state of adjuvant therapy for breast cancer.

Breast Neoplasms↗
PubMed2000

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.

Adult↗
PubMed2000

Risks and benefits of taxanes in breast and ovarian cancer.

The taxanes are a unique class of agents with a broad spectrum of clinical activity. They act by binding to tubulin, producing unnaturally stable microtubules and subsequent cell death. The distribution and elimination of paclitaxel depend on dose and administration rate. This nonlinearity is much less evident at lower infusion rates (24-hour infusions) and more evident at high plasma concentrations (3-hour infusions). The pharmacokinetics of docetaxel also suggest the presence of nonlinear pathways, but these appear to be clinically insignificant at the current doses utilised (60 to 100 mg/m2). Both agents undergo hepatic metabolism and biliary excretion and require dose adjustment in the setting of liver dysfunction. Drug interactions are quite common with these agents, some of which are sequence-dependent and clinically significant. The optimal dose of paclitaxel is not known at this time, and controversy over possible dose- or schedule-related differences in efficacy still remain. Docetaxel is somewhat more consistent in its dose and scheduling information, but controversy remains regarding a dose-benefit relationship as well as scheduling differences (weekly vs every 3 weeks). Toxicity profiles for these agents are somewhat different. Paclitaxel is more likely to be associated with peripheral neuropathy and myalgias/arthralgias than docetaxel. Docetaxel is more likely to be associated with a cumulative fluid retention syndrome that can be dose limiting. Paclitaxel and docetaxel are both highly active agents against breast cancer, including tumours that are resistant to anthracyclines. Docetaxel tends to have higher response rates overall, but direct comparisons at maximally tolerated doses have not been completed. Combination regimens with many different agents are attempting to improve on the responses seen with single-agent taxanes. The combination of paclitaxel and a platinum compound should be utilised as first-line therapy of advanced ovarian cancer. Controversy lies in the choice of the platinum compound and the dose and administration schedule of paclitaxel. Substitution of docetaxel for paclitaxel in these platinum-containing regimens is also being investigated. The taxanes also exhibit activity against ovarian cancer in patients previously exposed to platinum agents. These agents may also be administered intraperitoneally for local therapy of metastatic ovarian cancer. Although docetaxel and paclitaxel are often considered similar in activity and tolerability, this review emphasises the fact that these agents are indeed different. Clinicians need to be familiar with the benefits and adverse events related to each agent in order to make informed, appropriate clinical decisions.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Markers of bone resorption in patients treated with pamidronate.

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest difference as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 finished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical significance (P = 0.07) while the proportions with bony disease progression were significant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion.

Aged↗
PubMed1998

Update on endocrine therapy for breast cancer.

The choice of endocrine agent for breast cancer depends on the menopausal status of the patient, the stage of disease, prognostic factors, and the toxicity profile of the agent. Endocrine therapies are typically given sequentially, with the least toxic therapy given first. Tamoxifen is considered first-line endocrine therapy for all stages of breast cancer. New antiestrogens in development include nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens. Luteinizing hormone-releasing hormone agonists are an effective form of endocrine therapy for premenopausal women with advanced breast cancer, and aromatase inhibitors are effective in postmenopausal women. Newer and more selective aromatase inhibitors that are p.o. active and have improved side-effect profiles have been developed. Recent trials have found these agents to improve survival in comparison to the progestins; thus, aromatase inhibitors are replacing progestins as second-line therapy for metastatic disease. Current trials are examining the potential role of aromatase inhibitors as first-line therapy for metastatic disease or as adjuvant therapy for early disease. The antiprogestins and antiandrogens studied thus far have had only limited success in breast cancer clinical trials.

Antineoplastic Agents, Hormonal↗
PubMed1997

Progressive decrease in nuclear retinoic acid receptor beta messenger RNA level during breast carcinogenesis.

Some of the nuclear retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (RXRs) alpha, beta, and gamma are thought to mediate the effects of retinoids on cell growth, differentiation, and apoptosis and thereby prevent breast carcinogenesis. We analyzed the expression of mRNAs for the three RARs and RXR-alpha in histological sections of specimens from 70 breast cancer patients, which included adjacent normal tissue, ductal carcinoma in situ, and invasive cancer, using in situ hybridization. RARs alpha, beta, and gamma and RXR-alpha were expressed in 98.1, 98.0, 93.0, and 100% of the adjacent normal tissues. Significant decreases in the number of cases expressing RAR-beta were observed among ductal carcinoma in situ (83.1%) and invasive carcinomas (51.6%), especially among the poorly differentiated cases (77.4 and 35.7 %, respectively). No relationship was found between the expression of estrogen receptor and RAR-beta. These results implicate decreases in RAR-beta expression in breast cancer development and suggest that they are independent of estrogen receptor status.

Breast↗
PubMed1997

Chemotherapy-induced neutropenia and fever in patients with metastatic breast carcinoma receiving salvage chemotherapy.

BACKGROUND: Chemotherapy-induced neutropenia and associated fever and infection are the most common complications of systemic chemotherapy. In this retrospective analysis, the authors evaluated the incidence of neutropenic fever, infection, and mortality in relation to the level of neutropenia, performance status, course number of chemotherapy, bone marrow metastasis, and age among patients with metastatic breast carcinoma receiving salvage chemotherapy. METHODS: A total of 174 patients with previously treated metastatic breast carcinoma enrolled on 4 consecutive Phase II protocols were evaluated. RESULTS: Twenty-three percent of the patients had an episode of neutropenic fever (41 episodes among 40 patients). The incidence of neutropenic fever did not increase until the absolute neutrophil count (ANC) had decreased to less than 500/microL, and then fever incidence had a linear relationship with decreasing ANC (linear trend, P < 0.01). A source of infection was documented in 59% of the neutropenic fever episodes. The incidence of infection did not increase significantly until the ANC had decreased to less than 250/microL (P < 0.01). The risk of neutropenic fever and infection was also significantly higher when patients had poor performance status or were undergoing the initial courses of chemotherapy. Patients with bone marrow metastases also had a higher frequency of fever, infection, and death, but these differences were not statistically significant. CONCLUSIONS: For patients with metastatic breast carcinoma receiving salvage chemotherapy, the risk of fever increases with decreasing ANC, but the risk of infection does not increase significantly until ANC decreases to less than 250/microL. Poor performance status, initial courses of chemotherapy, and bone marrow metastases further increase the risk of fever, infection, and death.

Adult↗
PubMed1997

Phase II study of semisynthetic paclitaxel in metastatic breast cancer.

The aim of this phase II study was to characterise the efficacy and toxicity of semisynthetic paclitaxel in patients with metastatic breast cancer. Eligible patients had measurable disease and had been treated with one prior chemotherapy regimen either as adjuvant or for metastatic disease. Semisynthetic paclitaxel was given at a dose of 175 mg/m2 over 3 h every 21 days with dexamethasone, cimetidine and diphenhydramine premedications. 31 patients were entered. All were evaluable for toxicity. 30 patients were evaluable for response because 1 patient was lost to follow-up after receiving one cycle. One patient achieved a complete response and 10 patients achieved partial responses for an overall response rate (CR + PR) of 37% (95% confidence interval 20-56%). 17 patients (55%) experienced at least one episode of grade 3 or 4 neutropenia. There were two episodes of febrile neutropenia complicating 155 cycles of therapy. One of these resulted in a treatment-related death in a patient with pulmonary metastasis. 3 patients required dose reductions for grade 3 sensory neuropathy. Our study shows that the antitumour activity and toxic effects of semisynthetic paclitaxel appear to be identical to the naturally occurring product.

Adult↗
PubMed1997

Use of Truquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with stage II and stage III disease.

PURPOSE: The Truquant BR radioimmunoassay (RIA) (Biomira Diagnostics Inc, Rexdale, Canada) uses the monoclonal antibody B27.29 to quantitate the MUC-1 gene product (CA 27.29 antigen) in serum. We evaluated CA 27.29 antigen in a controlled, prospective clinical trial for its ability to predict relapse in stage II and stage III breast cancer patients. PATIENTS AND METHODS: Over a 2-year period, 166 patients who had completed therapy for stage II (80.1%) or III (19.9%) breast cancer and were clinically free of disease were serially tested for CA 27.29 antigen levels. The study was double-masked and cancer recurrence was documented based on clinical findings. Patients with two consecutive CA 27.29 antigen test results above the upper limit of normal were considered positive. RESULTS: The Truquant BR RIA had a sensitivity of 57.7%, specificity of 97.9%, positive predictive value of 83.3%, and negative predictive value of 92.6%. The recurrence rate was 15.7%. A Cox regression analysis showed that the only variable to correlate with recurrent disease was the CA 27.29 antigen test result. Patients with a positive test result had increased odds of having a recurrence (odds ratio, 6.8; P < .00001). The test was effective in predicting recurrence in patients with both distant and locoregional disease. In a subgroup of patients with bone pain, CA 27.29 antigen level was found to identify reliably patients who would subsequently develop recurrent disease. CONCLUSION: These data demonstrate that the Truquant BR RIA can be used as an aid to predict recurrent breast cancer in patients with stage II and III disease.

Adult↗
PubMed1997

Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer.

Relapse following complete remission achieved with a single course of high-dose chemotherapy continues to be the main cause of treatment failure in patients with metastatic breast cancer. A phase I/II trial was initiated that combined the two most active drugs against breast cancer, doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with cyclophosphamide, and delivered four cycles of these drugs with peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating factor support in an outpatient setting. Patients with untreated metastatic breast cancer received two cycles of doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2. During recovery from the second cycle, PBPCs were harvested. Responding patients were then admitted for a day to receive escalating-dose doxorubicin, paclitaxel, and cyclophosphamide followed by PBPC reinfusion on day 3 as outpatients. Seventeen patients have been enrolled to date. Ten patients completed treatment and received 34 cycles of high-dose chemotherapy every 21 days (range, 21 to 28 days). The median age was 47 years (range, 26 to 56 years) and the median number of metastatic sites was two (range, one to three). Five patients had received adjuvant chemotherapy (four cyclophosphamide/methotrexate/5-fluorouracil and one mitoxantrone-based). The most common toxic reactions were nausea and vomiting (75% of courses) and neurosensory (50% of courses). No patients had a decreased ejection fraction or overt congestive heart failure. Ten patients underwent cardiac biopsy (median doxorubicin, 253 mg/m2; range, 120 to 312 mg/m2); only one showed grade 1 cytotoxic changes with doxorubicin 240 mg/ m2. Six patients were admitted for neutropenic fever. Eight of 10 patients responded (two pathologically confirmed complete remissions in liver). At these doses, four cycles of doxorubicin, paclitaxel, and cyclophosphamide with PBPC and granulocyte colony-stimulating factor support every 21 days was well tolerated and showed evidence of activity. Enrollment at higher dose levels continues so that maximum tolerated dose can be defined.

Adult↗