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Biomedical subjects

F A Holmes

Publications and source records attributed to F A Holmes.

69 records · Page 4Linked to original sources
PubMed1989

Phase II evaluation of gallium nitrate by continuous infusion in breast cancer.

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 tinnitus 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.

Adult↗
PubMed1989

Consequences of breast irradiation in patients with pre-existing collagen vascular diseases.

Exaggerated acute and late effects were observed in three of four women with pre-existing collagen vascular disease (CVD) within 2 years after definitive megavoltage radiation therapy for breast carcinoma. Five women with breast carcinoma, who developed CVD 3 months to 10 years after radiation therapy, had no complications. An abnormally severe reaction was observed during treatment of one patient with discoid lupus. The patient developed moist desquamation that persisted for a month, requiring early termination of treatment. One year after treatment, the patient developed paresthesias in the ipsilateral arm. A planned reduction of the prescribed dose in a second patient with progressive systemic sclerosis did not prevent intense erythema at the end of treatment, followed 14 months later by chest wall necrosis, which eventually required multiple surgeries including chest wall resections. The third patient, who had systemic lupus erythematosis, developed necrosis 2 years after treatment, which progressed over 12 years to osteoradionecrosis of the clavicle, sternum and rib cage. Multiple surgeries to repair the defect were complicated by flap necrosis and pleurocutaneous fistulas. The fourth patient died 6 months after radiotherapy without apparent sequelae. None of the patients had evidence of recurrent carcinoma. A history of collagen vascular disease appears to be a contraindication to breast conservation or for elective irradiation for breast cancer.

Adult↗
PubMed1988

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy.

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

Adult↗
PubMed1988

Adjuvant therapy of breast cancer with or without additional treatment with alternate drugs.

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. All therapy was completed within 1 year. The estimated disease-free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor-positive tumors, disease-free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Sequential multiagent chemotherapy incorporating cisplatin, doxorubicin, and cyclophosphamide in the treatment of metastatic breast cancer.

Forty-three consecutive patients with metastatic breast cancer and clearly measurable disease were treated with sequential multiagent chemotherapy. Therapy consisted of the administration in fixed sequence of cisplatin, doxorubicin, and cyclophosphamide (PAC) (four cycles), vinblastine, doxorubicin, and dexamethasone (VAD) (six cycles), and VP-16, methotrexate, and 5-fluorouracil (VMF) (six cycles). At the conclusion of 16 cycles of chemotherapy, all treatment was stopped. Patients were assessed for toxicity and disease response after each treatment. Duration of response and survival rate were determined for 41 evaluable patients. The overall response rate was 80% with 24% complete responses, 15% to PAC alone. Median duration of response (8 months) and median survival (17 months) were not superior to other reported multiagent chemotherapeutic programs. Toxicity included neutropenic fever, sepsis, renal failure, and electrolyte imbalance. Administration of sequential multiagent chemotherapy with a cisplatin-containing combination did not improve response rate, complete responses (CR), duration of response, or survival in this group of previously untreated breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Cisplatin in combination with continuous infusion vinblastine for refractory breast cancer.

We assessed antitumor activity and toxic effects of cisplatin and 5-day continuous infusion vinblastine in 25 evaluable patients with metastatic breast carcinoma refractory to one or more chemotherapeutic regimens. We administered cisplatin at 70 mg/m2 i.v. followed by vinblastine 1.5 mg/m2 daily for five consecutive days. In our heavily pretreated, poor performance patient population, we observed one complete response and four partial responses, with a median time to progression of 35 weeks. Toxic effects were significant and prevented dosage escalation. The addition of cisplatin does not appear to improve the therapeutic value of vinblastine alone.

Adult↗
PubMed1987

Syndrome of inappropriate antidiuretic hormone secretion associated with hepatic arterial infusion of vinblastine in three patients with breast cancer.

We report the occurrence of the syndrome of inappropriate antidiuretic hormone secretion in 3 patients with breast carcinoma metastatic to the liver who received hepatic arterial infusion of vinblastine at lower doses than those previously associated with this effect. Leukopenia was severe in all patients, who additionally experienced hypokalemia with excessive kaliuresis. The etiology of the observed hypokalemia is unclear. We suspect that vinblastine may induce renal tubular dysfunction. These toxicities appear dose-related.

Adult↗
PubMed1987

Mitoxantrone, cyclophosphamide, and fluorouracil in metastatic breast cancer unresponsive to hormonal therapy.

Fifty-two patients with hormonally unresponsive or estrogen receptor negative metastatic breast cancer who had not received prior chemotherapy received mitoxantrone 10 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 1000 mg/m2 (MCF) by short intravenous infusion every 21 days. Disease that was resistant or stable to this regimen was treated with doxorubicin 25 mg/m2/day for two days and vinblastine 1.4 mg/m2/day for four days (DV). Both drugs were given by continuous infusion. Thirty-one partial remissions and four complete remissions occurred after treatment with MCF. Only thirty-four evaluable patients crossed to the DV phase with partial remission (11 patients), stable (five patients), or resistant (18 patients) disease. Eleven patients' responses were upgraded. The median overall time to progression (TTP), defined as the sum of the TTP on MCF and TTP on DV, was 12 months. The median survival of all patients was 19 months. Granulocytopenia was the dose limiting toxicity for MCF, but cumulative thrombocytopenia was noted. Nausea and vomiting occurred in most patients but was mild. Severe alopecia occurred in half the patients. One patient developed congestive heart failure after receiving a cumulative dose of 206 mg/m2 of mitoxantrone. The incidence of infectious complications was 35% on each regimen; 50% of these were mild. MCF is an effective combination that was well tolerated. Objective responses, durations of response, and survival were similar, but not superior, to standard doxorubicin-based combinations. Toxicity was somewhat less.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Syncope and hypotension due to carcinoma of the breast metastatic to the carotid sinus.

Tumors involving the carotid sinus and glossopharyngeal nerve may produce syncope due to bradycardia and hypotension. Carotid sinus syncope unrelated to cancer is usually caused by bradycardia and responds to control of the heart rate. When neoplastic disease involves the carotid sinus, vasodepressor hypotension, with or without bradycardia, is more common. Control of the heart rate alone is not effective. Although this syndrome is not common, it is probably not recognized in milder forms. Most patients in whom this syndrome develops have cancer of the head and neck. A patient with breast carcinoma metastatic to the neck and carotid sinus is described in whom syncope with hypotension and bradycardia developed. Although a temporary cardiac pacemaker controlled bradycardia, severe hypotensive episodes recurred despite treatment with anticholinergic and sympathomimetic drugs. The pathophysiology and therapy of this syndrome in patients with cancer are reviewed.

Aged↗
PubMed1987

Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients.

We assessed the efficacy of local fibrinolytic therapy in 35 axillary-subclavian vein thromboses (SVT) that occurred in cancer patients with percutaneous central venous catheters (CVC). These catheters were indwelling for a median of 1 month (range, one day to 10 months) before thrombosis developed. Urokinase was administered at a dose of 500 to 2,000 U/kg/h. Complete lysis occurred in 25 of 30 thrombi that were directly infused, after a median of four days. Complete lysis occurred in one of 12 thrombi that could not be directly infused with urokinase and in two of six with associated phlebitis. Eighty-one percent of the thrombi that were symptomatic for less than 1 week before treatment resolved, compared with 56% present for longer than 1 week. Sixteen patients who had complete (12) or partial (four) thrombolysis did not have their CVCs removed. All four patients with partial thrombolysis had recurrent thrombosis at a median of eight days (range, one to 90). Only two patients who had complete thrombolysis had recurrent thrombosis, at 8 and 16 months. Only minor hemorrhagic toxicity was seen.

Adult↗
PubMed1987

Phase II study of iproplatin in metastatic breast carcinoma.

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.

Adult↗
PubMed1986

Subclinical hepatic toxicity during combination chemotherapy for breast cancer.

We evaluated serial liver function tests (LFT) and serial liver imaging procedures for 190 consecutive patients with breast carcinoma to assess the incidence and severity of hepatic abnormalities during treatment with combination chemotherapy. Thirty-four percent of patients receiving adjuvant chemotherapy and 52% of patients being treated for metastatic breast cancer had one or more LFT abnormalities before initiation of therapy. Among patients with normal baseline LFT results, 77% of those receiving adjuvant chemotherapy and 82% being treated for metastatic breast cancer developed LFT abnormalities during therapy. Liver function test abnormalities were mild to moderate and never led to interruption of treatment; they appeared within the first three months of chemotherapy and normalized in 90% within one year of cessation of treatment. Our analysis suggests that LFT abnormalities detected during the administration of chemotherapy for patients with breast cancer are a manifestation of drug toxicity and that such abnormalities are insufficient evidence of hepatic metastases.

Alkaline Phosphatase↗
PubMed1986

A comparative study of bisantrene given by two dose schedules in patients with metastatic breast cancer.

Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status, dominant disease site, and response to prior doxorubicin therapy. All but one patient had received prior doxorubicin. Partial remission (PR) was achieved by 5 of 35 patients (14%) in the S arm and 7 of 35 patients (20%) in the D X 5 arm (P = NS). There were 4 patients who had primary refractoriness to doxorubicin but responded to bisantrene. The median number of courses was two for both arms. The median time to progression was 5 months for the responders in each arm and 3 and 4 months, respectively, for patients who showed no change in the S and D X 5 arms. Myelo-suppression was dose-limiting and greater for the D X 5 arm. Drug fever (34% versus 21% of courses; P = 0.02) and myalgia (22% versus 10% of courses; P = 0.02) were reported more often in the D X 5 arm; malaise was greater in the S arm. Grade 2-3 nausea and vomiting occurred more often in the S arm (40% versus 10% of courses; P less than 0.01). Significant hypotension that was not symptomatic occurred in 1 patient in the D X 5 arm. Phlebitis occurred in 3 patients without a central line. One patient who had previously received doxorubicin and mitomycin C developed heart failure, which was controlled with medication. Bisantrene is an effective drug for metastatic breast cancer that has incomplete cross resistance to doxorubicin, and there was no schedule dependency in this study.

Adult↗
PubMed1984

Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormonally unresponsive metastatic breast cancer.

Fifty-five patients with newly diagnosed, estrogen receptor negative, metastatic breast cancer were entered in a trial of mitoxantrone, 10 mg/m2 intravenous (IV), cyclophosphamide, 500 mg/m2 IV, and 5-fluorouracil, 1000 mg/m2 IV, which were given on day 1 of a 21-day treatment interval. This trial was designed to test the efficacy of substituting mitoxantrone for doxorubicin as part of a combination that has proved to be effective in inducing remission. The trial was also intended to evaluate the response of resistant disease and of stable metastatic disease to a combination of doxorubicin and vinblastine sulfate. The cardiotoxic potential of mitoxantrone was evaluated in all the patients by serial measurements of ejection fraction and by endocardial biopsy of the right ventricle. Patients who achieved a complete response or a partial response (with bone as the only site of disease) on the three-drug combination were continued on this treatment for 2 years, or for 1 year following a complete response, whichever was shorter or as cardiac monitoring permitted. Therapy with doxorubicin, 25 mg/m2/d for two days, followed by continuous infusion vinblastine sulfate, 1.4 mg/m2/d for four days, was given to all patients who progressed after two courses or were stable after six courses of three-drug therapy. The preliminary results from 50 patients show that 4 attained a complete response and 30 a partial response, giving a total response rate of 68%. The median duration of response was more than 7 months (range greater than 5 to greater than 15 months). One patient in complete remission relapsed after 8 months and failed reinduction therapy with doxorubicin-vinblastine sulfate. Myelosuppression, principally granulocytopenia, was the major side effect of cyclophosphamide-mitoxantrone-5-fluorouracil. Mild to moderate vomiting occurred in 76% of patients and alopecia in 88%. This therapy was discontinued in four patients because of a decreased cardiac ejection fraction and/or symptoms of heart failure. No cardiac biopsy score, however, has been greater than 1.0. These results suggest that a combination of cyclophosphamide-mitoxantrone-5-fluorouracil is effective in untreated, estrogen receptor negative, metastatic breast cancer and is comparable to the doxorubicin combination. Myocardial injury occurs with mitoxantrone, and a safe cumulative dose has yet to be established.

Adult↗