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F A Holmes

Publications and source records attributed to F A Holmes.

At least 37 records · Page 2Linked to original sources
PubMed1997

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer.

The first phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in breast cancer was completed at M.D. Anderson Cancer Center, and included 25 patients with metastatic breast cancer who had been previously treated with one chemotherapy regimen. Fourteen of these patients achieved a major objective response; the median response duration was 9 months, and the median survival time, 20 months. Additional trials showed that paclitaxel maintained its antitumor efficacy in patients with two and three prior chemotherapy regimens, including patients with anthracycline-resistant breast cancer. Combination therapy with doxorubicin showed that this combination was effective, although with the long infusion duration used for both agents, sequence-dependent toxic interactions were encountered. In combination with vinorelbine, dose-limiting toxicity included neutropenic fever and neuropathy. High-dose single-agent paclitaxel is currently being explored in the management of inflammatory breast cancer and as part of neoadjuvant chemotherapy for stages II and III operable disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Combination chemotherapy with paclitaxel and doxorubicin for metastatic breast cancer.

The development of anthracycline/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combinations has gone through several phases or generations. The first dose escalation studies used prolonged infusions of doxorubicin (48 to 72 hours) and paclitaxel (24 hours). Myelosuppression, mucositis, and neutropenic fever were dose limiting, and a sequence-dependent interaction was noted. In a second phase, doxorubicin was administered by bolus, without changing the schedule of the taxane. More recently, bolus doxorubicin was combined with 3-hour paclitaxel infusions. Higher doses of both agents were administered in this latter schedule, with higher overall response rates reported. Excessive cardiac toxicity was reported with the initial trials that used this schedule. Confirmatory studies are under way pursuing several alternatives to reduce the risk of cardiac toxicity; these include limiting the cumulative dose of doxorubicin, inserting an interval between the administration of the two drugs, and adding a cardioprotective agent to the combination. The high degree of antitumor activity of this combination is quite encouraging, and additional evaluation of this regimen in controlled trials is warranted in metastatic and high-risk primary breast cancer.

Antibiotics, Antineoplastic↗
PubMed1997

Prospective assessment of cardiac toxicity during a randomized phase II trial of doxorubicin and paclitaxel in metastatic breast cancer.

Since both doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have substantial antitumor activity in advanced breast cancer, the combination of these two agents was a logical extension of the clinical development of paclitaxel. Early attempts used long infusions of both drugs, limiting the dose of both agents because of limiting gastrointestinal and myelosuppressive toxicity. Bolus doxorubicin combined with 3-hour infusion paclitaxel was reported to have dramatic antitumor activity, but clinically relevant cardiac toxicity in up to 20% of patients in two recent reports. In our current study the same schedules and doses of administration were used, limiting the total doxorubicin dose of 360 mg/m2. In-depth monitoring of cardiac function with noninvasive tests and endomyocardial biopsy were performed. Preliminary results suggest that, at these doses and schedule, the two-drug combination is safe, without unexpected toxicity. Limiting doxorubicin dose to 360 mg/m2 limits cardiac toxicity to levels expected from single-agent doxorubicin at similar cumulative doses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer.

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed. The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without intervening disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2 has unacceptable toxic effects.

Adult↗
PubMed1996

A phase II study of CI-973 [SP-4-3(R)]-1,1-cyclobutane-dicarboxylato (2-)] (2-methyl-1,4-butanediamine-N, N') platinum in patients with refractory advanced breast cancer.

CI-973 is a water-soluble platinum diamine complex whose antitumor activity is greater than that of cisplatin in some murine tumors. It has shown activity against cisplatin-resistant tumors. This phase II trial had the objectives of determining the therapeutic efficacy of CI-973 in patients with metastatic breast cancer who had been treated with one prior chemotherapy regimen, and of further defining the toxicity of the agent and the reversibility of its toxicity. CI-973 was administered as an intravenous infusion over 30 min with no prehydration or antiemetic programs. Treatment cycles were repeated at 21-day intervals. Patients with histologically confirmed metastatic breast cancer, measurable disease, and good performance status who had received only one prior chemotherapy regimen for metastatic disease were eligible for treatment. Adequate hematologic, renal, and hepatic function were required. A total of 26 patients received a median of two courses of CI-973 (range, 1-18 courses). Hematologic toxicity was severe: nearly all patients experienced granulocytopenia with granulocyte counts of 0 at all dose levels. Nevertheless, neutropenic fever and documented systemic infection were uncommon, and there were no hospitalizations for neutropenic fever or infection. Visceral disease dominated in this patient group. Of the 26 patients, 14 had visceral disease, 6 had bone or bone marrow disease, and 6 had skin, soft-tissue, or lymph-node disease. Of the 26 patients treated, 25 were evaluable for response. There were two partial remissions, one in liver and one in bone, and three minor responses, for a response rate of 8%. Nonhematologic toxic effects were mild and consisted of nausea and vomiting, fatigue, minimum peripheral paresthesia, and hypomagnesemia. Further study of CI-973 at the dose and schedule used in this study is not warranted. Because this agent had no significant extramedullary toxicity, intensification of the dose of CI-973 with concomitant administration of colony-stimulating factors has the potential to improve response in this patient population.

Adult↗
PubMed1996

Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer.

PURPOSE: To determine whether a schedule-dependent interaction occurs when paclitaxel and doxorubicin are administered sequentially. PATIENTS AND METHODS: Ten patients with metastatic breast cancer received paclitaxel 125 mg/m2 over 24 hours either immediately before or after doxorubicin 48 mg/m2 over 48 hours as the initial chemotherapy treatment. Two such courses were given, and the sequence of administration was reversed after course 1. In cohort 1, paclitaxel preceded doxorubicin for course 1. In cohort 2, doxorubicin preceded paclitaxel for course 1. Doxorubicin levels were measured serially during the infusion and for 24 hours following it. Patients were assessed clinically for the occurrence of stomatitis and infection and granulocyte counts were measured twice weekly. RESULTS: Eight patients had complete pharmacokinetic sampling for both courses. The mean end-of-infusion plasma doxorubicin concentrations (Cmax) were 70% higher in the paclitaxel-doxorubicin sequence compared with the reverse sequence (45 +/- 8 ng/mL v 26 +/- 5 ng/ mL). The mean doxorubicin clearance was 32% lower in the paclitaxel-doxorubicin sequence (34.3 +/- 10.3 L/h v 51.6 +/- 16.1 L/h, P < .01). Clinically, hematologic and mucosal toxic effects were worse in the paclitaxel-doxorubicin sequence. The median absolute granulocyte count was 0.2/microL in the paclitaxel-doxorubicin sequence and 1.3/microL in the doxorubicin-paclitaxel sequence. Seven of 10 patients who received the paclitaxel-doxorubicin sequence had grade 2 (n = 4) or 3 (n = 3) stomatitis, while only one of 10 patients who received the doxorubicin-paclitaxel sequence had grade 2 stomatitis and none had grade 3. CONCLUSION: When paclitaxel by 24-hour infusion precedes doxorubicin by 48-hour infusion, doxorubicin clearance is reduced by nearly one third, which results in grade 2 and 3 stomatitis. To prevent this effect when paclitaxel (by 24-hour infusion) and doxorubicin are administered sequentially, doxorubicin should be given first. The mechanisms for this effect are under investigation.

Adult↗
PubMed1996

Single-agent paclitaxel for the treatment of breast cancer: an overview.

Initial trials using a 24-hour intravenous infusion of 250 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of breast cancer yielded objective regression in 56% to 62% of patients with no or only one prior chemotherapy regimen. Tolerance to single-agent paclitaxel seemed acceptable, but after multiple cycles, peripheral neuropathy developed in a significant fraction of patients. Lower doses and, more recently, the 3-hour infusion schedule still produced objective responses, albeit lower, in the range of 20% to 35%. It became apparent that toxicity was dose and schedule dependent, and likely there was a dose-response correlation. A 96-hour infusion schedule yielded a maximum tolerated dose of 140 mg/m2, and no hypersensitivity reactions despite omission of the standard triple-drug premedication. More recently, a 1-hour infusion schedule (plus standard triple-drug premedication) was well tolerated, with activity in both lung and breast cancer similar to that observed after a 3-hour infusion treatment. Paclitaxel retained therapeutic activity, even among patients with anthracycline-refractory breast cancer, in clinical trials using the 3-, 24-, and 96-hour infusion of paclitaxel. Current ongoing trials will explore the range of paclitaxel activity of various doses and by alternative schedules, both as second-line therapy and in the adjuvant and neoadjuvant setting.

Adult↗
PubMed1996

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review.

Combinations of active antineoplastic agents have been the most effective treatment for metastatic breast cancer. Criteria for an effective combination include use of drugs with different mechanisms of action, nonoverlapping toxic effects, and synergistic, or at least additive, antitumor activity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with its unique mechanism of action, offers an excellent opportunity for development of effective combination therapy against breast cancer. However, a number of problems have hindered the rapid development of effective combinations. The most obvious problem is the lack of a defined optimal dose and schedule of administration. The second problem has been the demonstration of unexpected interactions between paclitaxel and the other component(s) of the combination, often resulting in unusual and serious toxic effects. This review will focus on the phase I and II trials of paclitaxel in combination with established antineoplastic drugs (except doxorubicin and congeners, which is covered elsewhere in this issue) for breast cancer: cisplatin, 5-fluorouracil with or without folinic acid, cyclophosphamide, radiation therapy, as well as novel investigational agents or strategies, edatrexate, monoclonal antibodies to oncogenes, growth factors, and gene therapy with insertion of multidrug resistance gene into blood stem cells. Combination therapy offers exciting possibilities of enhanced antitumor efficacy. However, given the unexpected and serious toxic effects observed, only proven combinations should be used outside the context of a clinical trial. Additionally, the burden of proof will be to show that these combinations have increased antitumor activity, decreased toxicity, or both compared with single-agent paclitaxel.

Aminopterin↗
PubMed1996

Paclitaxel combination therapy in the treatment of metastatic breast cancer.

After the single-agent activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was confirmed, trials to develop a synergistic combination began. Doxorubicin, the most active agent for breast cancer, was studied first. As paclitaxel became more available, other combinations, including high-dose regimens and adjuvant therapies, have been studied. No optimal combination regimen has been defined. Recent and/or ongoing trials are looking at paclitaxel in combination with cisplatin, cyclophosphamide, 5-fluorouracil/ folinic acid, and mitoxantrone combinations, as well as with high-dose regimens and as adjuvant therapy. This review describes a plethora of combination studies finally under way to better define the optimal use of paclitaxel in breast cancer therapies, both as adjuvant treatment and for metastatic disease. Because of the unpredictable nature of drug interactions related to schedule and sequence, ad hoc combinations should not be undertaken outside the context of a well-designed trial.

Aminopterin↗
PubMed1995

Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.

PURPOSE: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

Adult↗
PubMed1995

Paclitaxel in the treatment of metastatic breast cancer: M.D. Anderson Cancer Center experience.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 250 mg/m2 by 24-hour infusion at 21-day intervals was evaluated at M.D. Anderson Cancer Center as a single agent in patients who had received one prior chemotherapy regimen either as adjuvant therapy or for metastatic disease. Of 25 patients treated, 12% had a complete remission and 44% had a partial response. The median time to progression was 9 months (range, 1 to 20 months). In the next phase of development, a phase I trial evaluated sequentially administered paclitaxel and doxorubicin as initial therapy for metastatic disease. Granulocyte colony-stimulating factor also was administered in each cycle. The dose-limiting toxicity was either stomatitis or neutropenic fever. The maximum tolerated dose (MTD) was 125 mg/m2 for paclitaxel and 48 mg/m2 for doxorubicin. Because of much lower than anticipated MTDs of both drugs in this schedule, it was hypothesized that there may be a schedule-dependent toxicity; therefore, in the second phase I study the schedule of administration was reversed (ie, doxorubicin followed by paclitaxel infusion). The MTDs of this schedule were 60 mg/m2 and 150 mg/m2 for doxorubicin and paclitaxel, respectively. Pharmacokinetic studies subsequently have confirmed that administration of paclitaxel before doxorubicin impairs the elimination of doxorubicin by some unknown mechanism. In an ongoing phase II study, paclitaxel is being evaluated in patients who have received three or more treatments with chemotherapy. Paclitaxel is administered at doses of 135 and 150 mg/m2 (for poor- and good-risk patients, respectively) without granulocyte colony-stimulating factor. Six patients (19%) have shown objective partial responses. Our initial phase II study showed significant antitumor activity for paclitaxel in patients who had received limited prior chemotherapy. Our phase I studies established that initial administration of paclitaxel alters the pharmacokinetics of doxorubicin and increases morbidity. The reverse sequence of administration was associated with better tolerance and a higher MTD. In heavily treated patients this drug also has significant antitumor activity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Update: the M.D. Anderson Cancer Center experience with paclitaxel in the management of breast carcinoma.

The first of three trials at M.D. Anderson Cancer Center investigating paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in metastatic breast cancer was a phase II study involving 25 patients (297 courses) previously treated with only one chemotherapy regimen; the patients received paclitaxel 250 mg/m2 infused over 24 hours without granulocyte colony-stimulating factor (G-CSF). Complete (12%) and partial responses (44%) led to median durations of response and survival of 9 and 21 months, respectively. The median paclitaxel dose was 200 mg/m2. Despite profound neutropenia (median granulocyte count of 0.3 cells x 10(9)/L for the first three courses), infection occurred in 42% of patients but only 6% of courses. In a phase I trial of paclitaxel 125 mg/m2 over 24 hours followed by doxorubicin 60 mg/m2 using G-CSF at 5 micrograms/kg days 5 through 19, dose-limiting mucositis with neutropenic fever occurred at the starting dose, so the maximum tolerated dose was one dose lower: paclitaxel 125 mg/m2 (over 24 hours) followed by doxorubicin 48 mg/m2 over 48 hours. Among 10 patients, there was one complete response and seven partial responses (overall response, 80%). Suspecting a schedule-dependent interaction between drugs, a phase I trial of the reverse sequence yielded a maximum tolerated dose, defined by neutropenic fever without mucositis, of doxorubicin 60 mg/m2 (over 48 hours) followed by paclitaxel 150 mg/m2 (over 24 hours) in 21 patients. A pharmacokinetic study in which the sequence of administration of paclitaxel over 24 hours and doxorubicin over 48 hours was alternated in courses 1 and 2 indicated that when paclitaxel by 24-hour infusion is given first, doxorubicin plasma levels at the end of infusion were an average 70% higher and doxorubicin clearance was reduced approximately 30% compared with the reverse sequence. Similarly, the incidence of grade 2 or 3 mucositis was 70% with the paclitaxel/doxorubicin sequence versus only 10% with the reverse sequence. We concluded that paclitaxel slows doxorubicin metabolism and that when used together in this schedule, doxorubicin should precede paclitaxel. In the third trial paclitaxel without G-CSF was administered to two groups of heavily pretreated patients: (1) those with only two prior chemotherapy regimens (inclusive of adjuvant therapy) received paclitaxel 175 mg/m2 over 24 hours and (2) those with three or more prior regimens received paclitaxel 150 mg/m2 over 24 hours. Response rates in both regimens were approximately 20%. We conclude that paclitaxel has significant antitumor activity in metastatic breast cancer, especially in patients with limited prior therapy, without need for G-CSF.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Phase I trial of droloxifene in patients with metastatic breast cancer.

Droloxifene (3-hydroxytamoxifen) is a new, nonsteroidal antiestrogen. In comparison with tamoxifen, it has a 10- to 64-fold higher affinity for the estrogen receptor and has shown a lower estrogenic and higher antiestrogenic effect in experimental studies. The objective of this study was to determine the toxicity (and its reversibility) of droloxifene given at different doses to patients with advanced metastatic breast cancer refractory to conventional endocrine therapy and chemotherapy. In this study, 30 patients were treated in groups of 6 at 5 different doses (20, 40, 100, 200, and 300 mg) by mouth once a day. Toxic effects included hot flashes, nausea, and fatigue and were not dose-related. Toxicity did not require any dose reduction or discontinuation of therapy. There was one episode of deep venous thrombosis and pulmonary embolism. There was no complete or partial response in this study, but four patients showed a minor response (13%). These data illustrate that this drug is well tolerated and needs to be further evaluated in phase II and III studies.

Adult↗
PubMed1994

Use of Taxol (paclitaxel) in breast cancer.

Taxol (paclitaxel) has demonstrated good antitumor activity against metastatic breast cancer (MBC) in phase II trials. The drug is usually well tolerated. However, severe myelosuppression, including rapidly reversible neutropenia, may necessitate dose reductions and may ultimately limit its use as a long-term treatment. Sequential or simultaneous administration of Taxol and doxorubicin may enhance response rates. There appears to be no complete cross-resistance between the two drugs. Current trials are exploring the best way to deliver this combination while keeping dose-limiting toxicity to a minimum. Additionally, single-agent trials are evaluating Taxol in extensively pretreated MBC. The results of these trials are awaited with interest.

Adult↗
PubMed1994

Bioequivalence of 20-mg once-daily tamoxifen relative to 10-mg twice-daily tamoxifen regimens for breast cancer.

PURPOSE: We studied the bioequivalence of a new once-daily regimen of tamoxifen citrate relative to the standard twice-daily regimen of tamoxifen citrate, an established antiestrogenic treatment for breast cancer. PATIENTS AND METHODS: Of 30 women with breast cancer, 27 completed this open, two-period, crossover randomized trial. During one 3-month period, patients took one standard 10-mg tamoxifen tablet twice daily; during the preceding or following 3-month period, patients took one of the new 20-mg tablets once daily. Pharmacokinetic profiles and safety parameters were assessed at the end of each 3-month treatment period. RESULTS: Overall, measured concentrations of tamoxifen and its principal active metabolite, N-desmethyltamoxifen, remained relatively constant over the 24-hour sampling periods at the end of each treatment sequence. For both compounds, the percentage differences of the geometric means for all pharmacokinetic parameters indicated bioequivalence of the once-daily regimen of tamoxifen relative to the standard twice-daily regimen. Both treatment sequences were well tolerated; reported adverse events occurred at similar frequencies with the two treatment regimens. CONCLUSION: The 20-mg tamoxifen tablet taken once daily was bioequivalent to the 10-mg tamoxifen tablet taken twice daily, with no difference in relative risk. The once-daily treatment is a simpler regimen and may facilitate compliance, which may enhance therapeutic outcomes during long-term treatment of breast cancer.

Administration, Oral↗
PubMed1994

Combination chemotherapy with Taxol (paclitaxel) in metastatic breast cancer.

In three phase I trials reported in the United States, the combination of paclitaxel and doxorubicin has been evaluated in previously untreated patients with metastic breast cancer. At M.D. Anderson Cancer Center, escalating doses of paclitaxel followed by a fixed dose of doxorubicin led to one complete remission (CR) and seven partial remissions (PRs) in 10 patients. Dose-limiting toxic effects were stomatitis and neutropenic fever. The maximum tolerated dose (MTD) was paclitaxel 125 mg/m2 and doxorubicin 48 mg/m2-lower than the starting dose. The reverse sequence (doxorubicin followed by paclitaxel) also was investigated to evaluate the possibility of schedule-dependent toxicity. The MTD of this reverse sequence was doxorubicin 60 mg/m2 and paclitaxel 150 mg/m2, with neutropenic fever as the dose-limiting toxicity. In a study by the National Cancer Institute (NCI), paclitaxel and doxorubicin were given simultaneously over 72 hours and doses of each were escalated resulting in two separate MTDs: paclitaxel/doxorubicin 160/75 and 180/60 mg/m2. Objective responses were 6% CR and 56% PR, and gastrointestinal disturbances were dose-limiting. Schedule-dependence also was addressed in a study at Indiana University, where the drug sequence was alternated for comparison both between and across patients. Preliminary results showed an increase in mucositis when paclitaxel was given before doxorubicin. It is concluded that this is an active combination and that schedule-dependent mucositis can be avoided if doxorubicin is given first. Myelosuppression is dose-limiting, even with granulocyte colony-stimulating factor, and thrombocytopenia occurs with multiple courses.

Adult↗
PubMed1993

The myeloprotective effect of recombinant human granulocyte-macrophage colony-stimulating factor given sequentially with continuous infusion vinblastine in metastatic breast cancer patients.

Colony-stimulating factors have been shown to have a myeloprotective effect when administered following chemotherapy. Chemotherapy of short duration with predominantly cell-cycle nonspecific agents has been most used. The myeloprotective effects of colony-stimulating factors given after cell-cycle specific or continuous infusion chemotherapy have not previously been assessed. Twenty-one evaluable patients with metastatic breast cancer progressing after one prior chemotherapy regimen were treated with continuous infusion vinblastine 2.0 mg/m2/day for 5 days. After the second chemotherapy cycle, granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for 10 days. Serial complete blood counts, differential, and platelet counts were obtained to document myelotoxicity. GM-CSF administration resulted in a significantly shorter duration of granulocytopenia, < 500/microliters, at the maximum GM-CSF dose. Significantly more rapid recovery of granulocytes to > 500/microliters, > 1000/microliters, and > 1500/microliters was seen with all doses and schedules of GM-CSF administered. The nadir absolute granulocyte counts were unaffected. GM-CSF given after continuous infusion cell-cycle specific chemotherapy is therefore myeloprotective.

Adult↗