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Biomedical subjects

A P Lyss

Publications and source records attributed to A P Lyss.

At least 19 recordsLinked to original sources
PubMed1995

Amonafide: An active agent in the treatment of previously untreated advanced breast cancer--a cancer and leukemia group B study (CALGB 8642).

Amonafide is a new imide derivative of naphthalic acid. The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials. The drug is extensively metabolized and detected in plasma and urine. Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CALGB) master metastatic breast cancer protocol. CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil, or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed. Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis. Amonafide was given at 300 mg/m2/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles. Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof. Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia. The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = <0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response. Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) with amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping.

Adenine↗
PubMed1993

Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.

PURPOSE: The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects. RESULTS: At 3 months, women treated with 160 mg/d reported less severe side effects (P < .0005), better physical functioning (FLS, P < .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life. CONCLUSION: Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.

Appetite↗
PubMed1992

Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B.

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intensive etoposide and carboplatin chemotherapy for advanced non-small-cell lung cancer. A phase II trial of the Cancer and Leukemia Group B.

From April 2 to July 9, 1989, Cancer and Leukemia Group B (CALGB) conducted a Phase II study of etoposide and carboplatin in advanced (AJC Stage IIIb-IV) non-small-cell lung cancer (NSCLC) patients whose performance status (PS) was 0-2. The combination was given at the maximum tolerated dose as defined in a prior CALGB study. Of 76 eligible patients with follow-up data, complete responses were achieved in three patients (4%) and partial responses, in five patients (7%). One patient (1%) with evaluable disease showed improvement. There was only one partial response in the PS 2 patients. Performance status was a predictive factor for response or improvement (p = 0.0368). A high incidence (74%) of severe or life-threatening hematologic toxicity and fatal sepsis in four patients was a reflection of the intensity of the chemotherapeutic regime. The median survival from study entry was 7.4 months. Thirty-seven percent of the patients survived beyond 1 year; the median survival for the PS 0-1 patients was 11.7 months for the PS 2 patients, 4.1 months. Median time to treatment failure was 3.9 months, but treatment had not failed in 9% of the patients after 1 year, all of whom were PS 0-1 at time of study entry. Although the response rate with this dose-intensive chemotherapy regimen was disappointing, the median survival of PS 0-1 patients was equivalent to that of Stage III NSCLC patients in prior CALGB studies. In patients with NSCLC who are treated with chemotherapy, PS may be as important a prognostic factor as stage, when median survival is used as an endpoint.

Adult↗
PubMed1992

Evaluation of an implantable venous access system in a general oncology population.

Venous access has been a problem for the practicing oncologist. Previous approaches, such as arteriovenous fistulas, grafts, or percutaneous catheters, have not gained widespread acceptability. We report our experiences with 230 Port-a-Cath devices, a totally implantable venous access system. The catheters were placed in 218 general oncology patients for the administration of chemotherapy. One patient had three catheters placed and 10 patients had two catheters each. Most patients received standard bolus chemotherapy, while 25 patients were treated with continuous ambulatory infusions. The catheters were in place for an average of 271 days (range 2-1,427 days) for a total of 62,330 catheter days, representing the largest published experience with devices of this type in cancer patients. A total of 24 complications occurred in 22 patients. Catheter insertion was associated with four pneumothoraces, two of which required chest tube drainage. Five catheters were removed because of infection. There were 6 cases of venous thrombosis, but none resulted in pulmonary embolism. Other complications were manageable and included catheter occlusion, migration, and extravasation of chemotherapy agents. The Port-a-Cath is safe and is associated with a low rate of complications. Implantable venous access systems represent a significant advantage in the management of oncology patients with poor venous access.

Catheters, Indwelling↗
PubMed1992

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience.

Since 1984, the Respiratory Committee of the Cancer and Leukemia Group B (CALGB) has evaluated carboplatin, either alone or in combination, in five separate phase II studies for patients with inoperable non-small cell lung cancer (NSCLC). All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had not received previous treatment with chemotherapy. In 70 patients with stage IIIB or IV disease, carboplatin 400 mg/m2 administered intravenously once every 4 weeks produced a 16% overall response rate and an acceptable toxicity profile. Subsequently, combinations of carboplatin/cisplatin, carboplatin/etoposide, and carboplatin/vinblastine have been evaluated in similar patient groups. Response rates of 11%, 12%, and 20%, respectively, were obtained. Myelosuppressive toxicity was substantially greater with carboplatin/etoposide and carboplatin/vinblastine than with carboplatin alone. Carboplatin/vinblastine demonstrated efficacy similar to that of the cisplatin/vinblastine combination previously evaluated by CALGB for treatment of similar patients with advanced NSCLC; ease of administration and lack of significant nephrotoxicity also compared favorably with cisplatin-based therapy. In regional NSCLC patients, carboplatin 100 mg/m2/wk can be administered intravenously concurrently with 60 Gy thoracic radiotherapy given over 6 weeks. The impact of concurrent carboplatin added to a sequential chemotherapy-radiotherapy program for patients with regional NSCLC is currently under study by the CALGB Respiratory Committee.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A simple method to estimate the initial dose of gentamicin.

A simple equation to estimate the initial dosing interval of gentamicin was compared with the "rule of eights" equation in 81 adult patients with stable renal function. The Sawchuk-Zaske method was employed as the standard with which dosing intervals estimated by the simple equation and the rule of eights method were compared. The actual mean peak gentamicin concentration was not significantly different from that predicted by the Sawchuk-Zaske method. The actual mean trough concentration was significantly higher than the predicted concentration, but trough concentrations within the usual therapeutic range of 0.5-2 microgram/ml were achieved in more than 90% of patients. The mean dosing interval calculated by Sawchuk-Zaske was not significantly different from that calculated by the equation, but was longer than the one calculated by the rule of eights. A peak gentamicin concentration within the usual therapeutic range was generally achieved with a total daily dose of 3-5 mg/kg of actual body weight. Until gentamicin concentrations are known, an easily remembered equation can be used to estimate the initial dosing interval for gentamicin. When used together with a standard total daily dose of 3-5 mg/kg total body weight, usual therapeutic concentrations are achieved in the majority of patients.

Adolescent↗
PubMed1991

Positron tomographic assessment of 16 alpha-[18F] fluoro-17 beta-estradiol uptake in metastatic breast carcinoma.

The positron-emitting estrogenic steroid 16 alpha-[18F]fluoro-17 beta-estradiol (FES) has been shown to exhibit selective uptake in primary breast carcinomas; the uptake of tracer by positron emission tomography (PET) is strongly correlated with the tumor estrogen-receptor concentration. We have now extended the use of this radiopharmaceutical for imaging of metastases of breast carcinoma by PET in 16 patients with clinical or radiographic evidence of metastatic disease. Increased uptake of FES was identified on PET images in 53 of 57 metastatic lesions (93%); only two apparent false-positive foci of FES uptake were seen. In seven of the patients, evaluable PET studies were obtained both before and after initiation of antiestrogen therapy. In all cases, there was a decrease in FES uptake in the tumor deposits after initiation of antiestrogen therapy, and the mean (+/- standard deviation) uptake decreased from 2.22 (+/- 1.23) to 0.80 (+/- 0.42) x 10(3)+ dose/ml. These results indicate that PET with FES has high sensitivity and specificity for detecting metastatic breast carcinoma and provide additional confirmatory evidence that the tumor uptake of this ligand is a receptor-mediated process.

Breast Neoplasms↗
PubMed1991

Management of soft tissue sarcomas of the extremities.

The management of soft tissue sarcomas has undergone and continues to undergo important changes. The purpose of this report is to review the presentation, diagnosis, and natural history of soft tissue sarcomas. In so doing, the importance of a careful and rigorous method of evaluation will be emphasized. Furthermore, the results of multidisciplinary treatment, with a goal towards limb salvage, will be reviewed. With appropriate and timely intervention, selected patients with pulmonary metastases may still experience long-term survival. Throughout this review, the importance of early and continuing multidisciplinary treatment and evaluation will be emphasized.

Arm↗
PubMed1989

Vindesine and mitomycin C in metastatic breast cancer. A Southeastern Cancer Study Group Trial.

64 eligible women with previously treated metastatic breast cancer received mitomycin C plus vindesine chemotherapy. Dosage was based on investigators' estimate of patients' bone marrow reserve. There were 19 evaluable patients in the good marrow reserve category, with two complete and three partial responses (26%). In the poor marrow reserve category there were 29 evaluable patients with four partial responses (14%). The 26% response rate in patients with good marrow reserve is consistent with results obtained with this and similar combinations by other investigators.

Adult↗
PubMed1988

Appendiceal malignancies.

Malignancies of the appendix are extremely rare. Of the reported cases, carcinoid tumors are most common, with mucinous cystadenocarcinomas and adenocarcinomas next in frequency. Adenocarcinoids, which share morphologic and clinical features that are a composite of adenocarcinomas and carcinoids, have been described. Concomitant second malignancies, most often in the GI tract, occur with greater than expected frequency in patients with appendiceal tumors. Treatment and prognosis are markedly different for each of the histologic variants of appendiceal malignancy. In general, carcinoid tumors (smaller than 2 cm in diameter) may be treated by appendectomy alone and are associated with long term survival. Adenocarcinomas, unless well differentiated and extremely superficial and localized, required hemicolectomy and confer a prognosis that is, stage for stage, similar to that of adenocarcinoma of the colon. Mucinous cystadenocarcinomas may spread widely through the abdomen, resulting in P peritonei, but can be associated with long survival duration if surgical treatment is aggressive. There is evidence that adenocarcinoids develop from simultaneous neoplastic change in two stem cell populations. Metastases may show histologic features of adenocarcinomas alone, of carcinoid tumors alone, or may resemble a composite neoplasm. The prognosis is variable and treatment recommendations are not well defined.

Adenocarcinoma↗
PubMed1987

Systemic treatment for prostate cancer.

Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo-hormonal therapy produces more favorable results than hormonal treatment alone.

Acid Phosphatase↗
PubMed1987

Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases.

Doxorubicin is a potent anticancer agent effective in a wide range of malignancies, but its use is limited by dose-dependent late cardiotoxicity. Severe doxorubicin cardiotoxicity has been associated with a poor prognosis and a high mortality rate, and until recently has been thought to be irreversible. We describe the cases of three patients with well-documented severe left ventricular dysfunction due to doxorubicin who had complete clinical recovery with return of cardiac function to normal. Because severe doxorubicin cardiotoxicity is reversible in some patients, aggressive supportive therapy is warranted.

Adult↗