[Show abstract][Hide abstract] ABSTRACT: Background:
Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with variable outcomes. This study was conducted to explore whether this combination was effective and tolerable in MBC patients who were heavily pretreated with anthracyclines and taxanes.
A phase I study was conducted first to establish the maximum tolerated dose (MTD) of the G and V combination in MBC patients. Then, a phase II study evaluated the response rates, the median time to progression (TTP), the overall survival (OS) as well as the toxicities resulting from this combination at the MTD.
Nine patients were enrolled in the phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25 patients involved in the phase II study were evaluable for response. No complete or partial responses were achieved; 6 patients (24.0%) had stable disease and 15 (60.0%) progressed. The median TTP was 2 months and the median OS 10 months. Grade 3/4 Neutropenia was the major hematologic toxicity, occurring in 52% of the cycles. The most common non-hematologic grade 3/4 toxicities were fatigue (18%), myalgias (17%) and arthralgias (13%).
In heavily pretreated patients with MBC, the combination of G and V at the doses stated above was ineffective as it did not induce partial or complete responses. Other chemotherapy agents or combinations should be evaluated in future studies.
Journal of Cancer 03/2014; 5(5):351-9. DOI:10.7150/jca.8304 · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the pathologic complete response (pCR) rate of patients treated with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide (FAC) versus dose-intense FAC plus G-CSF in the neoadjuvant setting and to compare the delivered dose intensity, disease-free survival (DFS) and overall survival (OS) times, and toxicity between treatment arms in patients with breast cancer.
Patients were randomized to receive preoperative FAC (5-FU, 500 mg/m(2); doxorubicin, 50 mg/m(2); cyclophosphamide, 500 mg/m(2)) every 21 days for four cycles or dose-intense FAC (5-FU, 600 mg/m(2); doxorubicin, 60 mg/m(2); cyclophosphamide, 1,000 mg/m(2)) plus G-CSF every 18 days for four cycles.
Two hundred two patients were randomly assigned. The median follow-up was 7.5 years. Patients randomized to FAC plus G-CSF had a higher pCR rate as well as clinical complete response rate; however, these differences were not statistically different from those with the FAC arm. Patients in the FAC + G-CSF arm had a higher delivered dose intensity of doxorubicin in the neoadjuvant and adjuvant settings than those in the standard FAC arm. DFS and OS times were not significantly different between the two groups. However, the OS and DFS rates were significantly higher for patients who achieved a pCR than for those who did not. Thrombocytopenia, febrile neutropenia, and infection rates were higher in the FAC + G-CSF arm.
A higher delivered dose intensity of doxorubicin with the FAC + G-CSF regimen did not result in a statistically significant higher pCR rate. However, patients who achieved a pCR experienced longer DFS and OS times.
The Oncologist 11/2011; 16(11):1527-34. DOI:10.1634/theoncologist.2011-0134 · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study sought to quantify the extent of downstaging after preoperative chemotherapy for stage III breast cancer, to assess the feasibility of breast-conserving therapy (BCT) after preoperative chemotherapy, to determine the effectiveness of this multimodal treatment as measured by disease-free survival (DFS) and overall survival (OS), and to evaluate toxicities.
Patients were treated with 4 preoperative courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). They were then evaluated for response to go to mastectomy or BCT. After local therapy, patients with an excellent response were treated with 4 additional cycles of FAC, whereas patients with a moderate response received 4 cycles of MV (methotrexate and vinblastine). A total of 203 patients were registered; 194 patients (96%) underwent surgery after chemotherapy.
The 5-year OS and progression-free survival rates were 89.8% and 81.6%, respectively, for patients with an excellent response to therapy compared with 67.2% and 63.5%, respectively, for patients with a moderate response and 55.3% and 48.8%, respectively, for patients considered nonresponders (P=.0005 for OS; P<.0001 for DFS). Cytopenia, nausea/vomiting, and stomatitis were the most common toxicities. Preoperative chemotherapy with FAC downstaged 88.6% of patients, and BCT was possible in >25%.
Response to preoperative chemotherapy was a prognostic factor in improved long-term survival.
Clinical Breast Cancer 12/2008; 8(6):516-21. DOI:10.3816/CBC.2008.n.063 · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This phase II trial was conducted to assess the efficacy and safety of 10-Ethyl-10-Deaza-Aminopterin (10-EDAM), a folate antagonist, in metastatic breast cancer patients who had received no more than one prior chemotherapy regimen.
Fifty-five patients were treated on an initial weekly dose 80 mg/m(2) of 10-EDAM. Patients who had received a prior chemotherapy regimen in the adjuvant setting (group 1) were considered separately from patients who had received a prior chemotherapy regimen in the metastatic setting (group 2).
The response rate for both groups combined was 18%, and median time to progression was 3 months. Median overall survival was 12 months. Treatment was associated with common chemotherapy-related toxicities, such as 25% grade three or four neutropenia and 20% grade three or four stomatitis.
In patients with metastatic breast cancer who had received one prior chemotherapy regimen, 10-EDAM was well tolerated. In general, while definite antitumor activity was documented, time to progression was brief.
Cancer Chemotherapy and Pharmacology 07/2007; 60(1):61-7. DOI:10.1007/s00280-006-0348-9 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this phase II study was to evaluate the efficacy and tolerability of Orathecin, an oral camptothecin analog that has exhibited antitumor activity in breast cancer patients during preclinical studies.
Sixteen patients with metastatic breast cancer previously treated with anthracycline and taxane were utilized in the study. Orathecin was administered orally at 1.5 mg/m2 /day for the first five consecutive days of the cycle followed by 2 days of rest on a 7-day schedule. The end points of the study were efficacy and toxicity.
The median age of the patients was 51 years (range, 35-73). Eight patients (50%) had multiple disease sites, and nine patients (56%) received more than three chemotherapy regimens. All patients were evaluated for toxicity, three patients were removed from the study for toxicity or disease progression prior to 8 weeks and were thus not evaluated for efficacy. The median follow-up was 110 days (range, 15-554). There were no responses to treatment. Five of the 13 evaluable patients (38%) had stable disease, eight (61%) had progressive disease. Most adverse events were mild to moderate in intensity. The median time to progression (TTP) for evaluable patients was 109 days (range, 56-374 days) (lower 95% C.I., 57 days). The median survival time was 272 days (lower 95% C.I., 209 days).
Orathecin at the dose and regimen used in this study resulted in no objective tumor responses for this heavily pretreated population. Accurate risk stratification strategies can improve patients' selection and contribute to determine the appropriate benefit of therapies in MBC.
Cancer Chemotherapy and Pharmacology 05/2006; 57(4):540-4. DOI:10.1007/s00280-005-0064-x · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The treatment of inflammatory breast cancer includes preoperative anthracycline-based chemotherapy, surgery, and radiation therapy. In the past few years, taxanes, mainly paclitaxel, have been frequently used for preoperative chemotherapy, usually in sequence with anthracyclines. The purpose of this retrospective analysis was to determine how adding paclitaxel to anthracycline-based regimens affects prognosis. A total of 240 patients treated in 6 consecutive trials between 1973 and 2000 were included in the analysis. Group 1 (N = 178) consisted of patients treated in the first 4 trials (1973-1993) with FAC (5-fluorouracil/doxorubicin/cyclophosphamide) based regimens. Group 2 (N = 62) consisted of patients treated in the last 2 trials (1994-2000) with FAC followed by paclitaxel given every 3 weeks or given in a high-dose weekly schedule. The 2 groups differed with respect to median follow-up durations, which were 148 months (range, 85-283 months) in group 1 and 45 months (range, 21-99 months) in group 2. Estrogen receptor (ER) status was negative in 58 cases (33%) in group 1 and 40 cases (65%) in group 2. There was no difference in median age between the groups. The objective response rates (complete and partial) were similar (group 1, 74%; group 2, 82%). The median overall survival (OS) and progression-free survival (PFS) were better in the patients treated with paclitaxel, and these differences reached statistical significance in the patients with ER-negative disease (median OS: group 1, 32 months; group 2, 54 months; P = 0.03; median PFS: group 1, 18 months; group 2, 27 months; P = 0.04). It may be concluded that the addition of paclitaxel to anthracycline-based therapy resulted in a statistically significant improvement in outcome in patients with ER-negative inflammatory breast cancer.
Clinical Breast Cancer 03/2004; 4(6):415-9. DOI:10.3816/CBC.2004.n.004 · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.
Clinical Cancer Research 11/2002; 8(11):3360-8. · 8.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation.
We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer.
The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P <.0001) and increasing combined clinical stage (P <.0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P =.0048), increasing number of involved lymph nodes (P <.0001), and no use of tamoxifen (P =.0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P <.001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P =.008), and no use of tamoxifen (hazard ratio of 3.9, P =.027) independently predicted for LRR.
Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.
Journal of Clinical Oncology 01/2002; 20(1):17-23. · 18.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine the clinical, pathological, and treatment factors that are predictive of local-regional recurrence and overall survival for patients with breast cancer that is refractory to neoadjuvant chemotherapy.
This study analyzed the data of the 177 breast cancer patients treated on our institutional protocols who had less than a partial response to neoadjuvant chemotherapy. The initial clinical stage of disease was II in 27%, III in 69%, and IV (supraclavicular lymph node involvement) in 4%. Surgery was performed in 94% of the patients, and 77% of these patients also received adjuvant chemotherapy.
After a median follow-up of 5.2 years, 106 patients experienced disease recurrence, with 98 of these having distant metastases and 45 having local-regional recurrence. The 5- and 10-year overall survivals for the entire group were 56% and 33%, respectively. The factors that were independently associated with a statistically significant poorer overall survival in a Cox regression analysis were pathologically involved lymph nodes after surgery, estrogen receptor-negative disease, and progressive disease during neoadjuvant chemotherapy. The 5-year overall survival for patients with pathologically negative lymph nodes ranged from 84% (estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative disease), compared with rates for patients with pathologically positive lymph nodes of 66% (estrogen receptor-positive disease) and 40% (estrogen receptor-negative disease). The 5-year survival of patients with progressive disease was only 19%. The 5- and 10-year local-regional recurrence rates for the 177 patients were 27% and 34%, respectively. Significant factors on Cox analysis that predicted for local-regional recurrence were four or more pathologically involved lymph nodes and estrogen receptor-negative disease. For the 105 patients treated with surgery and postoperative radiation therapy, the 10-year local-regional recurrence rates for the subgroups with 0, 1, or 2 of these factors were 12%, 25%, and 44%, respectively.
For patients with a poor response to neoadjuvant chemotherapy, conventional treatments achieve reasonable outcomes in those with lymph node-negative disease or estrogen receptor-positive disease. However, more active systemic and local therapies are needed for patients with estrogen receptor-negative disease and positive lymph nodes and for those with clinical evidence of progressive disease during neoadjuvant chemotherapy.
The Cancer Journal 09/2001; 7(5):413-20. · 4.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population.
Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated.
The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively).
In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.
Cancer 02/1999; 85(1):104-11. DOI:10.1002/(SICI)1097-0142(19990101)85:13.0.CO;2-R · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy.
Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates.
A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years.
This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.
Journal of Clinical Oncology 11/1997; 15(10):3171-7. · 18.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory
breast carcinoma. Patients and methods: A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center
by a combined-modality approach under four different protocols. Each protocol included induction chemotherapy, then local
therapy (radiotherapy or mastectomy), then adjuvant chemotherapy, and, if mastectomy was performed, adjuvant radiotherapy.
Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with or without vincristine and prednisone
(VP). In protocol D, patients received an alternate adjuvant chemotherapy regimen, methotrexate and vinblastine (MV), if they
did not have a complete response (CR) to induction chemotherapy. Results: The median follow-up of live patients in group A was 215 months, in group B 186 months, in group C 116 months, and in group
D 45 months. An estimated 28% of patients were currently free of disease beyond 15 years. At the time of analysis, 50 patients
were alive without any evidence of disease. A further 12 patients died of intercurrent illness, and 15 patients were followed
beyond 10 years without recurrence of disease. Among initial recurrence, 20% of patients had local failure, 39% systemic failure,
and 9% CNS recurrence. Initial response to induction chemotherapy was an important prognostic factor. Disease-free survival
(DFS) at 15 years was 44% in patients who had a CR to induction chemotherapy, 31% in those who had a partial response (PR),
and 7% in those who had less than a PR. There was no improvement in overall survival (OS) or DFS among patients who underwent
alternate chemotherapy (MV) compared with those who did not. Using surgery and radiotherapy as opposed to radiotherapy alone
as local therapy did not have an impact on the DFS or OS rate. Conclusion: These long-term follow-up data show that with a combined-modality approach a significant fraction of patients (28%) remained
free of disease beyond 15 years. In contrast, single-modality treatments yielded a DFS of less than 5%. Thus, using combined-modality
treatment (chemotherapy, then mastectomy, then chemotherapy and radiotherapy) is recommended as a standard of care for inflammatory
Cancer Chemotherapy and Pharmacology 05/1997; 40(4):321-329. DOI:10.1007/s002800050664 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the long-term clinical course of patients with metastatic breast cancer (MBC) who achieved a complete remission with doxorubicin-alkylating agent-containing combination chemotherapy programs.
To assess the long-term prognosis of MBC, we reviewed our experience with 1,581 patients treated on consecutive doxorubicin and alkylating agent-containing front-line treatment protocols between 1973 and 1982. Treatment was administered for a maximum duration of 2 years. Characteristics of long-term survivors were evaluated, and hazard rates for progression were calculated.
From this group, 263 (16.6%) achieved complete responses (CR) and 49 (3.1%) remained in CR for more than 5 years. After a median duration of 191 months, 26 patients remain in first CR, four patients died in CR at times ranging from 118 to 234 months, 18 patients died of breast cancer, and one is alive with metastatic disease. Compared with the overall CR and total patient populations, the long-term CR group had more premenopausal patients, a younger median age, a lower tumor burden, and better performance status. The hazard function shows a substantial drop in risk of progression after approximately 3 years from initiation of therapy. Ten long-term CR patients developed second primary cancers: breast (3), ovary (2), pancreas (1), endometrium (1), colon (1), head and neck (1), and lung (1).
Most patients with MBC treated with systemic therapies have only temporary responses to treatment, but some patients continue in CR following initial treatment. These data show that a small percentage of patients achieve long-term remissions with standard chemotherapy regimens. Remission consolidation strategies are needed.
Journal of Clinical Oncology 09/1996; 14(8):2197-205. · 18.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Seven hundred fifty-two patients with stage III disease (of those, 178 patients with inflammatory carcinoma) were treated with a combined modality approach at our institute in seven prospective studies. After three to four cycles of chemotherapy, each patient was treated with local therapy. An estimated 54% of patients with stage IIIA disease and 24% of patients with stage IIIB disease were free of disease. An estimated 30% of patients with inflammatory carcinoma of breast were free of disease beyond 10 years with this approach.
Surgical Oncology Clinics of North America 11/1995; 4(4):715-34. · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Clinical Oncology 05/1993; 16(2):132-6. DOI:10.1097/00000421-199304000-00010 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carcinoembryonic antigen (CEA) values in 529 patients treated in two consecutive adjuvant chemotherapy protocols were analyzed to determine if CEA values correlated with disease-free status or prognostic utility. CEA values were evaluated preoperatively, before chemotherapy, at the conclusion of chemotherapy, and during postchemotherapy followup. The sensitivity of CEA for predicting disease recurrence was low; however, any abnormal CEA at the conclusion of chemotherapy and during followup significantly correlated with reduced disease-free and overall survival. A CEA value greater than or equal to 20 ng/ml at the end of chemotherapy or during followup was highly specific and a strongly positive predictor for the presence of metastases. Abnormal CEA values before chemotherapy that became normal at the conclusion of chemotherapy were associated with a significantly reduced recurrence rate. An abnormal CEA value obtained before or after adjuvant chemotherapy is clinically useful and can provide prognostic information.
Cancer 04/1989; 63(5):828-35. DOI:10.1002/1097-0142(19890301)63:53.0.CO;2-3 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the role of gallium nitrate infusion in the treatment of metastatic breast cancer. Gallium nitrate was administered at 300 mg/m2/day for 7 days every 3 weeks by continuous infusion concomitantly with oral calcium supplement of 500 mg twice daily and oral hydration. Fifteen patients with refractory metastatic breast cancer received such treatment for a total of 30 courses. Median age was 51, and median performance status (Zubrod scale) was 1. These patients had minimal prior chemotherapy (median 1 regimen). All patients were evaluable for toxicity and 14 for response. Nine patients had one to two metastatic sites, five patients had three to four sites. No major objective response was seen, but one patient had a minor response (10 weeks), and another showed no change in disease (16 weeks). Diverse low-grade toxicities were observed, including nausea and vomiting in 11 patients, anorexia in 11, diarrhea in eight, stomatitis in five, dysgeusia in six, musculoskeletal pain in five, skin rash in seven, partially reversible tinnitis and/or mild hearing loss in four and sensory neuropathy in two. A consistent drop in hemoglobin (median of 3.2 g/dL per patient) necessitated blood transfusion in seven patients. There was no granulocytopenia or thrombocytopenia; however, significant lymphopenia was noted. Reversible, moderate nephrotoxicity occurred in two patients. The hypocalcemic effect was consistent, with a median drop in serum calcium of 1.25 mg/dL per course. There was no hepatic toxicity. While no single toxicity was severe, overall toxicity adversely influenced treatment tolerance. Gallium nitrate by continuous infusion, as given in this study, has no activity in metastatic breast cancer.
Investigational New Drugs 01/1989; 7(2):225-229. DOI:10.1007/BF00170863 · 2.92 Impact Factor