Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 37 records · Page 2Linked to original sources

PubMed2000

Gemcitabine and paclitaxel combination therapy in transitional cell carcinoma of the urothelium.

Transitional cell carcinoma (TCC) of the urothelium is considered a chemosensitive malignancy; however, few patients receiving standard therapies achieve long-term disease control. Thus, new treatment approaches using more effective and less toxic agents are needed to improve prognosis in these patients. Two new agents currently being studied are gemcitabine and the taxanes; both of which have produced overall response rates ranging from 22.5 to 28% (gemcitabine), and 7-56% (paclitaxel) when used as single agents in this disease. Both agents have been well tolerated. Results of two phase II studies of gemcitabine combined with paclitaxel have been published. In one, 60% (15/25) of evaluable patients with advanced stage IV TCC responded; in the other, 53% (8/15) of patients with advanced and/or metastatic TCC responded. Several trials evaluating different dosing regimens of gemcitabine plus paclitaxel or docetaxel are ongoing or planned.

Adult↗

PubMed2000

Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin.

PURPOSE: To evaluate the toxicity, response rate and short-term survival associated with the chemotherapy combinations of docetaxel plus cisplatin or carboplatin when used for the treatment of patients with metastatic carcinoma of unknown primary site. PATIENTS AND METHODS: Twenty-six patients were treated with docetaxel 75 mg/m2 i.v. and cisplatin 75 mg/m2 i.v. given every three weeks (study A) and subsequently, 47 patients were treated with docetaxel 65 mg/m2 and carboplatin (AUC dose = 6) every three weeks (study B). Stable or responding patients received a maximum of eight courses of therapy. Patients who were known to be in treatable subset groups were excluded from these trials. The majority of patients had two or more sites of metastasis; about 45% had adenocarcinoma and 50% poorly differentiated carcinoma. RESULTS: In study A, 6 of 23 (26%) assessable patients had a major response to therapy. The median survival was eight months and one-year survival 42%. Seven patients were removed from the study early for grade 3 or 4 nausea and vomiting. In study B, 9 of 40 assessable patients (22%) had a major response to therapy. Median survival was eight months and one-year survival 29%. Toxicity associated with this regimen was predominantly myelosuppression. Comparisons of the two sequential trials showed no differences in response rates or survivals (P = 0.75). CONCLUSIONS: Docetaxel and cisplatin (study A) is an active combination in carcinoma of unknown primary site, but associated with substantial gastrointestinal toxicity. A combination of docetaxel plus carboplatin (study B) is better tolerated and produced a similar response rate, median survival and one-year survival. Comparative phase III trials will be necessary to unequivically prove a survival advantage for any form of therapy in these patients. However, the survival for patients with carcinoma of unknown primary site receiving docetaxel-based chemotherapy is comparable to the survivals for several other groups of advanced cancer patients, such as non-small cell lung cancer, receiving various types of chemotherapy.

Adult↗

PubMed2000

Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site.

PURPOSE: To determine the frequency of Her-2 overexpression in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site. PATIENTS AND METHODS: Tumor specimens from 100 patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma were stained for the Her-2 protein using the Dako immunohistochemical method. Clinical and pathologic characteristics of patients with and without Her-2 overexpression were compared. RESULTS: Staining for Her-2 overexpression was successful in 94 of 100 patients. Ten (11%) of 94 tumor specimens overexpressed Her-2. Eight of 10 overexpressors had poorly differentiated adenocarcinoma, and all overexpressors had predominant tumor location above the diaphragm, usually in the mediastinum or lungs. CONCLUSION: Her-2 overexpression occurs in a minority of patients with poorly differentiated carcinoma/adenocarcinoma of unknown primary site. Because most overexpressors had poorly differentiated adenocarcinoma, further evaluation of patients with adenocarcinoma of unknown primary site is necessary to determine the frequency of Her-2 overexpression in this common subgroup. Evaluation of the efficacy of trastuzumab in Her-2 overexpressors with carcinoma of unknown primary site is indicated.

Adenocarcinoma↗

PubMed2000

Abnormal erythrocyte anion exchange in Alzheimer disease.

CONTEXT: Several abnormalities have been described in red blood cells of patients with Alzheimer disease (AD), but to date none of these has been confirmed by a second, independent study. Erythrocyte anion exchange has been reported to be abnormal in AD; we have developed a new technique for measuring anion exchange. OBJECTIVES: To confirm the abnormality of erythrocyte anion exchange in AD and to determine whether the phenomenon has potential for clinical utility. DESIGN: Comparison of patients with probable AD to age-matched controls. SETTING: University hospital and ambulatory clinic. METHODS: Chloride-bicarbonate exchange was measured in erythrocyte ghosts resealed with a fluorescent probe of chloride concentration. RESULTS: Erythrocyte anion exchange is abnormal in AD. This difference appears in citrate but not EDTA anticoagulant. Mahalanobis's generalized distance between the 2 populations is 1.7, and a discriminant function derived from our technique classifies 82% of the study population in accordance with the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Receiver operating characteristic analysis demonstrates the possibility of choosing cutoffs with high sensitivity and specificity. CONCLUSIONS: Measurement of red blood cell anion exchange may be useful in classifying patients with AD. The dependence of this phenomenon on anticoagulant suggests the involvement of platelet activation or complement fixation.

Adult↗

PubMed2000

Phase II trial evaluating triplet chemotherapy using gemcitabine, paclitaxel, and carboplatin in the treatment of patients with advanced non-small cell lung cancer.

The purpose of this study was to evaluate the combination of gemcitabine, paclitaxel, and carboplatin in patients with advanced non-small cell lung cancer. Previously untreated patients with stage IIIB or IV non-small cell lung cancer were enrolled into this trial. Sixty-nine patients from the phase II portion and eight patients from the phase I portion were treated with gemcitabine 1,000 mg/m2 intravenously on days I and 8, paclitaxel 200 mg/m2 as a 1-hour infusion on day 1, and carboplatin at an area under the curve of 5.0 intravenously on day 1. Treatment courses were repeated every 21 days. The phase II component of the study was completed at 13 community-based practices in the Minnie Pearl Cancer Research Network. Thirty-four of 71 fully evaluable patients had an objective response (48%, two complete and 32 partial responses). Twenty-five patients (35%) were stable and 12 (17%) progressed. The median response duration was 6 months (range, 3 to 14 months) and the median survival was 9.9 months, with 1- and 2-year survival rates of 47% and 21%, respectively. The combination of gemcitabine, paclitaxel, and carboplatin has been shown to be safe and effective; thus, this three-drug regimen will be compared with a standard two-drug regimen, paclitaxel/carboplatin, in a phase III study.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Management of patients with cancer of unknown primary site.

Cancer of unknown primary site represents approximately 3% to 5% of all new cancer diagnoses. Adenocarcinomas account for 60% of all unknown primary cancers and poorly differentiated carcinomas or adenocarcinomas, for 30%. Historically, the prognosis for most patients with unknown primary tumors has been poor, with survival often less than 6 months from diagnosis. Recent advances in diagnostic techniques, including immunocytochemical and molecular genetic methods, have increased the probability of identifying a likely underlying tumor type. Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. In these patients, favorable prognostic factors for treatment response include tumor location in lymph nodes, fewer sites of metastases, younger age, and poorly differentiated carcinoma histology. Although experience remains limited, the incorporation of a taxane into empiric regimens appears to improve response rates and survival. A recent study of paclitaxel (Taxol), carboplatin (Paraplatin), and etoposide in 55 patients with cancer of unknown primary site reported an overall response rate of 47% and a median overall survival of 13.4 months. Investigations continue to explore new diagnostic techniques and novel therapeutic approaches.

Adenocarcinoma↗

PubMed2000

Gemcitabine, paclitaxel, and carboplatin for advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the combination of gemcitabine (Gemzar), paclitaxel (Taxol), and carboplatin (Paraplatin) in patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients with stage IIIB or IV NSCLC were included in this trial. A total of 69 patients from the phase II portion and 8 patients from the phase I portion were treated with gemcitabine 1,000 mg/m2 intravenously (i.v.) on days 1 and 8; paclitaxel 200 mg/m2 as a 1-hour infusion on day 1; and carboplatin at an area under the curve (AUC) dose of 5.0 i.v. on day 1. Treatment courses were repeated every 21 days. The phase II component of the study was completed at 13 community-based practices within the Minnie Pearl Cancer Research Network. Of the 71 fully evaluable patients, 34 had an objective response, for an overall response rate of 48%; 2 patients showed complete responses and 32 patients had partial responses. A total of 25 (35%) patients were stable and 12 (17%) patients progressed. The median response duration was 6 months (range 3 to 14 months), and the median survival was 9.9 months, with a 1-year survival of 47% and a 2-year survival of 21%. These results show that the combination of gemcitabine, paclitaxel, and carboplatin is safe and effective; however, randomized phase III studies are needed to prove this regimen is superior to other regimens.

Adenocarcinoma↗

PubMed1999

Phase I/II trial of paclitaxel by 1-hour infusion, carboplatin, and gemcitabine in the treatment of patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The combination of paclitaxel and carboplatin is widely used in the treatment of patients with advanced nonsmall cell lung carcinoma. In this Phase I/II study the authors evaluated the feasibility, toxicity, and efficacy of adding a third active antineoplastic agent, gemcitabine, to the paclitaxel/carboplatin combination for the treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Patients with advanced (AJCC Stage IIIB or IV) nonsmall cell lung carcinoma previously untreated with chemotherapy were eligible for this trial. The maximum tolerated doses, determined in the Phase I trial and subsequently used in the Phase II trial, were: paclitaxel, 200 mg/m2, as a 1-hour infusion on Day 1; carboplatin, at area under the curve dose of 5.0 intravenously (i.v.), on Day 1; and gemcitabine, 1000 mg/m2 i.v., on Days 1 and 8. Treatment courses were repeated every 21 days. The Phase II study was conducted in 13 community-based practices in the Minnie Pearl Cancer Research Network; 77 patients were treated between December 1996 and September 1997. RESULTS: Thirty-four of 77 patients (44%) in the Phase II trial had major responses (partial responses, 32 patients and complete responses, 2 patients). An additional 25 patients (33%) had stable disease or minor response; only 23% of patients progressed or were removed from study at or prior to first reevaluation. The median survival was 9.4 months, with a 45% actuarial 1-year survival rate. Myelosuppression was the most common toxicity, with Grade 3/4 NCI Common Toxicity Criteria leukopenia and thrombocytopenia in 49% and 45% of patients, respectively. However, only 11 patients (14%) required hospitalization for neutropenia/ fever, and none had bleeding complications. Grade 3/4 nonhematologic toxicities included fatigue (41%), arthralgias/myalgias (26%), peripheral neuropathy (8%), nausea/emesis (6%), and hypersensitivity reactions (4%). There was one treatment-related death due to sepsis. CONCLUSIONS: This three-drug regimen is active and has acceptable toxicity in patients with advanced nonsmall cell lung carcinoma. Myelosuppression, particularly thrombocytopenia, is increased in comparison to the paclitaxel/carboplatin regimen. Fatigue also may be increased, but other nonhematologic toxicities are not altered substantially by adding gemcitabine. Although the response rate and median survival are improved modestly compared with our previous experience with paclitaxel/carboplatin, definitive conclusions regarding the efficacy of this regimen await the completion of randomized trials.

Adult↗

PubMed1999

Phase I trial of paclitaxel, carboplatin, and topotecan with or without filgrastim (granulocyte-colony stimulating factor) in the treatment of patients with advanced, refractory cancer.

BACKGROUND: Topotecan is a new antineoplastic agent with a broad spectrum of activity. The purpose of this Phase I trial was to define the maximum tolerated dose of topotecan when added to the widely used combination of paclitaxel and carboplatin. METHODS: Patients with advanced cancer that was refractory or resistant to standard treatments were treated with paclitaxel, carboplatin, and topotecan; doses were escalated in sequential cohorts of patients. After definition of the maximum tolerated dose without cytokines, granulocyte-colony stimulating factor (G-CSF) was added and further dose escalation was attempted. RESULTS: The maximum tolerated doses were: paclitaxel, 135 mg/m2, as a 1-hour intravenous (i.v.) infusion on Day 1; carboplatin, area under the curve 5.0, on Day 1; and topotecan, 0.75 mg/m2, i.v. on Days 1, 2, and 3; the regimen was repeated every 21 days. Myelosuppression, particularly thrombocytopenia, was the dose-limiting toxicity with this three-drug combination. Nonhematologic toxicity was uncommon. The addition of G-CSF did not allow substantial dose escalation because thrombocytopenia was uneffected by this agent. Eleven of 25 patients had major responses to this combination, including 8 of 14 patients with previously treated small cell lung carcinoma. CONCLUSIONS: The combination of paclitaxel, carboplatin, and topotecan is feasible, although only relatively low doses of all three drugs can be tolerated due to myelosuppression. This regimen showed a high level of activity in these patients with refractory cancer, and merits further investigation.

Adult↗

PubMed1999

Paclitaxel-based therapy in non-small-cell lung cancer: improved third generation chemotherapy.

The newer or 'third generation' chemotherapeutic agents (paclitaxel, docetaxel, vinorelbine, gemcitabine, irinotecan, topotecan) have all recently been shown to have substantial activity against non-small-cell lung cancer (NSCLC). Many of these agents are now being incorporated into the therapy for patients with advanced disease. Paclitaxel was the first 'third generation' drug to be studied. The use of paclitaxel and carboplatin has proven to be a well tolerated and quite active regimen with one-year survival in patients with stage IV disease of about 40% and two-year survival of about 20%. These survival rates are at least twice as good as previous platinum-based regimens. We have simplified the administration of paclitaxel by using a one-hour infusion and many other investigators and clinicians have followed suit. The results are equivalent to a three-hour infusion schedule. Given the degree of activity in patients with stage IV disease, it is imperative to begin neoadjuvant and adjuvant trials with the newer drugs and drug combinations. We and others have started a neoadjuvant strategy which has proven to be feasible and most patients tolerate surgery well. While the results are quite preliminary, we have seen some complete pathologic responses (about 20%) and are encouraged by these early data. In addition, we have routinely used adjuvant paclitaxel and carboplatin in patients with stage IB-IIIA disease who have been previously resected. Radiotherapy and a weekly schedule of paclitaxel and carboplatin have been incorporated for patients with stages II-IIIB (selected IIIB patients). Randomized comparisons are certainly needed in the neoadjuvant and adjuvant arena and the other 'third generation' drugs need to be quickly evaluated. We have chosen to add a third agent to paclitaxel and carboplatin. The evaluation of several triple combinations including the addition of gemcitabine, vinorelbine and topotecan, respectively to the paclitaxel-carboplatin combination has been completed. Preliminary results from these trials will be briefly summarized and plans for additional studies of the newer agents will also be discussed. Studies to learn the appropriate combinations, doses and schedules of the newer drugs in concert with radiotherapy and/or resection are also urgently needed. Since the newer 'third generation' drugs appear to genuinely improve the survival of patients with stage IV disease, it is likely that incorporation of these more active agents into therapy for lower stages of disease will make an even greater impact on overall survival for patients with this common neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Adjuvant dose-intense chemotherapy with peripheral blood stem cell support in stage II-III breast cancer with five to nine involved axillary lymph nodes.

The purpose of this study is to determine outcomes for patients with high-risk nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral blood stem cell support. Forty-three patients with stage II-III disease, five to nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60 years) were enrolled in a study that included: 1) standard dose doxorubicin, 5-fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide, filgrastim, and peripheral blood stem cell harvest; and 3) high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two patients (74%) are alive, 28 (65%) without relapse at a median of 55 months (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian catheter complication after etoposide and late radiation pneumonitis), and nine other deaths (21%) were associated with recurrent breast cancer. The probabilities of overall and event-free survival at 4 years were 0.77 and 0.67, respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients with 10 or more positive axillary nodes receiving the same sequence of therapy. Thus, patients with five to nine positive axillary lymph nodes have a similar risk of failure after high-dose chemotherapy and peripheral blood stem cell support as patients with 10 or more positive axillary lymph nodes.

Adult↗

PubMed1999

Oral etoposide in lymphoma.

Etoposide is one of the most active agents for the therapy of lymphomas. Oral etoposide has proven to be active in and clearly beneficial for patients with previously treated lymphomas. The optimal dose and schedule of oral etoposide for use in combination chemotherapy are still uncertain, but low daily doses (50 to 100 mg) for 10 to 14 days may be near optimal. Studies in previously untreated patients using combination chemotherapy that includes oral etoposide are needed, since preliminary data suggest that this agent has excellent activity and tolerability when combined or alternated with methotrexate, calcium folinate (calcium leucovorin), cyclophosphamide, vincristine, and prednisone in the elderly and medically unfit patient. Combination therapy approaches may also be helpful in HIV-related lymphomas. Additional studies are warranted.

Administration, Oral↗

PubMed1999

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer.

When combination regimens containing a platinum compound and etoposide are used, median survivals in patients with extensive- and limited-stage small cell lung cancer are 7 to 10 months and 15 to 20 months, respectively. A recent randomized trial demonstrated equivalent efficacy and decreased toxicity with carboplatin/etoposide compared with cisplatin/etoposide. Because of excellent single-agent activity, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been recently added to various platinum/etoposide combinations. Phase I/II studies with paclitaxel/cisplatin/etoposide and paclitaxel/carboplatin/etoposide have demonstrated excellent activity with acceptable toxicity. Ongoing phase III trials will better define the contribution of paclitaxel to standard platinum/etoposide regimens. In addition, phase II trials of novel paclitaxel combinations (e.g., paclitaxel/topotecan, paclitaxel/carboplatin/topotecan) are ongoing.

Antineoplastic Agents, Phytogenic↗

PubMed1999

The evolving role of paclitaxel for patients with carcinoma of unknown primary site.

Patients with carcinoma of unknown primary site represent a very heterogeneous clinicopathologic group. Progress has been made in defining important clinical subsets, and specialized pathologic analysis is essential for the poorly differentiated neoplasms. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a broad-spectrum antineoplastic agent with demonstrated activity in a wide variety of carcinomas. We have combined paclitaxel with carboplatin and oral etoposide for the therapy of patients with unknown primary carcinoma. The overall response rate (47%, with 13% complete responders) compares favorably with any other chemotherapy. Furthermore, the median survival of 13.4 months was notable and encouraging. Toxicity was well-tolerated and no treatment-related deaths occurred. Additional data are needed to more firmly establish the role of paclitaxel for unknown primary cancer.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Weekly administration of docetaxel (Taxotere): summary of clinical data.

Docetaxel (Taxotere; Rhône-Poulence Rorer, Antony, France) is a highly efficacious antineoplastic agent; however, its administration every 3 weeks produces substantial myelosuppression. Based on recent observations that the administration of paclitaxel on a weekly schedule minimizes myelosuppression, investigation of weekly docetaxel has been initiated. A recently completed phase I study of weekly docetaxel demonstrates markedly decreased myelosuppression with this schedule. The maximum tolerated dose was 43 mg/m2/wk; with this dose, myelosuppression was mild and the dose-limiting toxicity was fatigue/asthenia. Other nonhematologic toxicities were uncommon when doses of less than 40 mg/m2/wk were administered. Edema was not observed, in spite of an abbreviated dexamethasone schedule (8 mg every 12 hours for three doses, beginning 12 hours before docetaxel). A 50% response rate using docetaxel 35 to 40 mg/m2/wk has been achieved in patients with metastatic breast cancer. When used concurrently with radiation therapy, weekly scheduling allowed a maximization of docetaxel dosing, with the maximum tolerated dose being 20 mg/m2/wk. It is likely that this novel schedule of docetaxel will allow the drug to be used with decreased toxicity and will facilitate its incorporation into active combination regimens. Further investigation of this novel schedule of administration is warranted.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Docetaxel (Taxotere) administered in weekly schedules.

The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study. This finding was similar to that in another phase I/II trial of weekly docetaxel in previously treated patients with metastatic breast cancer in which the recommended dose for the phase II study was 35 mg/m2. In this latter study, an objective response rate of 50% and a 0% incidence of febrile neutropenia have been reported. Other studies have been conducted to evaluate the efficacy and safety of the weekly schedule. One such study is an ongoing phase II trial in elderly or medically unfit patients with previously untreated advanced non-small cell lung cancer in whom weekly docetaxel appears active and well tolerated. Further investigation of weekly docetaxel alone or in combination is warranted.

Adult↗

PubMed1998

One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial.

The aim of this phase II study was to determine the activity and toxicity of paclitaxel (administered by 1-h infusion) and carboplatin in advanced non-small cell lung cancer when used in a multicentre, community-based treatment setting. 100 chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer were treated between March 1995 and February 1996. All patients had Karnofsky performance status 70-100, measurable disease and adequate bone marrow, kidney and liver function. All patients received intravenous (i.v.) paclitaxel 225 mg/m2 by 1-h infusion followed immediately by carboplatin at a targeted area under the concentration time curve (AUC) of 6.0 using the Calvert formula. Courses were repeated every 21 days. Colony stimulating factors were not used routinely. 38 of 94 evaluable patients (40%) had objective responses to treatment (3 complete responses, 35 partial responses). An additional 32 patients had stable disease at initial re-evaluation. Weight gain during treatment was experienced by 47% of patients with objective response or stable disease. The median survival in this group of 100 patients was 8 months, with an actuarial 1-year survival of 42%. Leucopenia was common, but hospitalisation for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy was common, but usually appeared after the third or fourth course and was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. There was one treatment-related death due to sepsis. This large multicentre community-based phase II trial demonstrated the efficacy of paclitaxel and carboplatin combination chemotherapy in advanced non-small cell lung cancer. When paclitaxel is given by 1-h infusion, this regimen is easily administered in the outpatient setting.

Adult↗

PubMed1998

Mobilization and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim.

The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 microg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 microg/ kg. The median number of CD34+ cells collected after 10 microg/ kg (n = 31) was 0.7 x 10(6)/kg/apheresis (range 0.1-4.4) as compared to 1.2 (range 0.1-6.8) after 30 microg/kg (n = 32) (P = 0.04). Among patients randomized to 10 v 30 microg/kg, more (50%) achieved > or = 5.0 x 10(6) CD34+ cells/kg and less aphereses were required to achieve > or = 2.5 x 10(6) CD34+ cells/kg after the higher dose (P = 0.04). In multivariate analyses, patients receiving 10 microg/kg (n = 31) had lower yields of CD34+ cells (P = 0.026) and had a 3.3-fold increase in the probability of not achieving > or = 5.0 x 10(6) CD34+ cells/kg as compared to patients receiving 20-40 microg/kg (n = 59). Patients who had received radiation had a 2.9-fold probability of not achieving > or = 2.5 x 10(6) CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 microg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.

Antigens, CD34↗