Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: The Hoosier Oncology Group has previously reported the results of its phase II trial of the combination of cisplatin plus gemcitabine. In that study of 27 assessable patients with advanced or metastatic non-small-cell lung cancer (NSCLC), the response rate was 33%, with a median survival of 8.4 months. Based on such favorable results, the Hoosier Oncology Group designed this randomized phase III study of gemcitabine plus cisplatin compared with cisplatin alone in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients were randomized to receive either cisplatin (100 mg/m(2) intravenously on day 1 of a 28-day cycle) or the combination of cisplatin (100 mg/m(2) intravenously on day 1) plus gemcitabine (1,000 mg/m(2) administered intravenously on days 1, 8, and 15 of a 28-day cycle). RESULTS: From August 1995 to February 1997, 522 assessable chemotherapy-naive patients were randomized. Toxicity was predominantly hematologic and was more pronounced in the combination arm, with grade 4 neutropenia occurring in 35.3% of patients compared with 1.2% of patients on the cisplatin monotherapy arm. The incidence of neutropenic fevers was less than 5% in both arms. Grade 4 thrombocytopenia occurred in 25. 4% of patients on the combination arm compared with 0.8% of patients on the cisplatin monotherapy arm. No serious hemorrhagic events related to thrombocytopenia were reported for either arm. The combination of gemcitabine plus cisplatin demonstrated a significant improvement over single-agent cisplatin with regard to response rate (30.4% compared with 11.1%, respectively; P <.0001), median time to progressive disease (5.6 months compared with 3.7 months, respectively; P =.0013), and overall survival (9.1 months compared with 7.6 months, respectively; P =.004). CONCLUSIONS: For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.

Acute circulatory and respiratory collapse in obstetrical patients: a case report and review of the literature.

Venous air embolism is the entrapment of air into the venous system producing signs and symptoms due to obstruction of pulmonary arterial blood flow. We present a healthy, 27-year-old, full-term parturient admitted for postdate induction of labor. Cesarean delivery was required following fetal distress. During delivery, the mother became bradycardic and required advanced cardiac life support for resuscitation. Serial hemoglobin values, electrocardiograms, echocardiograms, and a magnetic resonance image of the head were all normal. No fetal squamous cells were found in the patient's blood. She required 6 days of ventilation, was successfully extubated, and was discharged 14 days after the cesarean delivery. The differential diagnosis in this patient's care centered on a pulmonary embolic event. Thromboembolism was unlikely, based upon the patient's rapid clinical improvement without definitive therapy for thrombotic disease or detection of peripheral thrombosis. Amniotic fluid embolus was unlikely, although not excluded, by the absence of fetal cells in the maternal circulation and the lack of an accompanying intravascular coagulopathy. Air embolism may occur in up to 50% of women undergoing cesarean delivery. A lethal embolism may follow a bolus of 3 to 5 mL/kg of air. Chief among the many symptoms of air embolism are tachypnea, chest pain, and gasping. The diagnosis may be facilitated by precordial Doppler monitoring, transesophageal echocardiography, or by the identification of air when aspirating from a right heart catheter. Management includes optimum patient positioning, aspiration of air, discontinuation of nitrous oxide, administration of 100% oxygen, and flooding the surgical site with saline to avoid further air entry. Preventive strategies are also discussed.

Outcome of advanced stage low grade follicular lymphomas in a population-based retrospective cohort.

BACKGROUND: To the authors' knowledge previous reports of patient outcome for advanced stage low grade follicular lymphomas (LGFL) have not been population-based. This is the first report describing the outcome of these patients based on a population-based cohort. METHODS: A retrospective chart review was performed for all patients diagnosed with advanced stage LGFL between 1987-1995 for the adult population of central and northern Alberta, Canada. RESULTS: One hundred and fifty-seven patients were diagnosed with advanced stage LGFL. Approximately 45% of patients had died at last follow-up. Treatment was initiated at the time of diagnosis in 87 patients (55%), with alkylating agents used in 66% of them. Of the 70 patients not treated at the initial diagnosis, 69% had been treated at a median of 16.3 months. The overall median survival was 5.9 years. On univariate analysis, significant variables (P < 0.20) included age, B symptoms, symptomatic lymphadenopathy, symptomatic splenomegaly, splenomegaly, Eastern Cooperative Oncology Group performance status, baseline lactate dehydrogenase (LDH), diffuse component on histology, and treatment at the time of diagnosis. By multivariate analysis, the only factors that influenced survival significantly and independently were baseline LDH and B symptoms. An elevated baseline LDH had a hazard ratio of 2.80 (95% confidence interval [CI], 1.65, 4.74) and a median survival of 8.0 years versus 3.6 years (P < 0.0001). B symptoms had a hazard ratio of 2.30 (95% CI, 1.23, 4.30) and a median survival of 6.5 years versus 3.1 years (P < 0.0067). CONCLUSIONS: Although some patients with advanced stage LGFL enjoy a prolonged survival, 80% of deaths in this cohort were attributable to lymphoma. The median overall survival of 5.9 years offers a less positive perspective on the outcome of these patients than in previous nonpopulation-based reports. This emphasizes the need for further population-based studies as well as new therapeutic approaches, especially those directed toward patients with poor prognostic features such as elevated baseline LDH and B symptoms.

Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.

PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.

Feasibility study of replacement procedures and earthquake perfomance related to gas transmission pipelines

A detailed and systematic review of the seismic perfomance of gas transmission lines prior to the 1994 Northridge earthquake shows that all repairs in pipelines affected by traveling ground waves occurred in areas which experienced seismic intensities of MMI>/ VIII. A review of gas transmission line perfomance during the 1994 Northridge earthquake discloses a similar pattern of seismic response. Approximately 91

of all pipeline damage caused by traveling ground waves in the 1994 event occurred in areas with MMI>/VIII. The earthquake-related damage has been predominantly in the form of ruptures at oxy-acetylene girth welds. The potential for damage in such welds appears to increase considerably for seismic intensities equal to and greater than MM VIII.(AU)

The Northridge, California earthquake of january 17, 1994 : Perfomance of gas transmission pipelines

On January 17,. 1994 at 4:31 a.m., a magnitude 6.6 earthquake struck the Los Angeles metropolitan area. Epicentered in the San Fernando Valley town of Northridge, California, the earthquake caused serious damage to buildings and sections of elevated freeways; ignited at least one hundred fires as it ruptured gas pipelines; and disrupted water supply systems. As a consequence, 57 people died, another 1,500 were seriously injured, and 22,000 were left homeless. Over 3,000 buildings, most of which were residential structures, were declared unsafe for reentry due to earthquake damage. Los Angeles, a city which has extensively prepared itself for earthquakes, found that it had experienced the most destructive event since the 1906 San Francisco earthquake. Direct economic losses are estimated currently at over $20 billion. This reconnaissance report provides a perfomance analysis of gas transmission lines, both during this earthquake and during previous earthquakes, in Southern California.(AU)

Earthquake perfomance of gas transmission pipelines

Over 61 years of earthquake perfomance of steel transmission pipelines operated by the Southrn California Gas Company are reviewed. The seismic record includes 11 major earthquakes with ML >= 5.8 and epicenters within the transmission system. An evaluation is made of the most vulnerable types of piping, failure mechanisms, break statistics, threshold seismic intensity to cause failure, and damage induced by permanent ground displacement. The database assembled represents one of the most comprehensive and detailed records of seismic response in a large, complex gas transmission system.(AU)

Novel, dose intensive, single-agent cisplatin in the first-line management of advanced stage ovarian cancer.

Cisplatin-based combination chemotherapy is the current standard chemotherapy for the management of advanced stage, epithelial ovarian cancer. However, correlation has been demonstrated previously between dose intensity and response for cisplatin, but not for the other cytotoxic drugs commonly used. We treated 46 consecutive, newly diagnosed patients following standard debulking laparotomy with cisplatin 60 mg m-2 every 2 weeks for a total of 8 cycles. Survival and toxicity were compared with those of a similar cohort of 24 consecutive, newly diagnosed patients treated with cisplatin 75 mg m-2 plus cyclophosphamide 600 mg m-2 every 4 weeks for 6 cycles, at the same institution immediately prior to the current cohort. The single-agent cisplatin cohort received a mean relative cisplatin-equivalent dose intensity of 1.43 compared with a received mean relative cisplatin-equivalent dose intensity of 0.88 in the combination chemotherapy cohort, a 62.5% increase in the cisplatin dose intensity. At 2 years, 69% of the patients receiving single-agent cisplatin were alive, compared with 38% of the group receiving the combination chemotherapy (P = 0.014). Alopecia (P < 0.00001) and myelosuppression (P < 0.0000001) were markedly less in the patient group receiving single-agent cisplatin. There was no significant difference in the incidence of neurotoxicity (P = 0.28) or nephrotoxicity (P = 0.38) between the two patient groups. In summary, relatively dose intensive, single-agent cisplatin given in a biweekly schedule for the first-line management of advanced stage, ovarian cancer produced a survival advantage compared with the previous combination cyclophosphamide/platinum combination chemotherapy. This novel therapy takes one-third less time to complete and causes fewer side effects than the current standard of combination cyclophosphamide and cisplatin.

Testicular seminoma associated with the acquired immunodeficiency syndrome and acquired immunodeficiency syndrome related complex: 2 case reports.

Two homosexual men positive for human immunodeficiency virus with evidence of acquired cellular immunodeficiency were diagnosed recently to have seminoma of the testis. One man has the acquired immunodeficiency syndrome with lymphopenia, a low CD4:CD8 ratio, condylomata accuminata, pneumocystis carinii and cerebral toxoplasmosis, and 1 has an acquired immunodeficiency syndrome related complex with generalized lymphadenopathy showing follicular hyperplasia on biopsy, recurrent Herpes simplex infections and lymphopenia but a supranormal CD4:CD8 ratio. Neither patient has a known risk factor for testicular seminoma. Our report provides supportive evidence for the presence of an increased risk of seminoma of the testis in patients with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome related complex.

High grade nonHodgkin's lymphoma: management with moderate dose combination chemotherapy.

We have reviewed the management of high grade nonHodgkin's lymphoma in a regional cancer centre over an eight year period. Forty-seven patients were referred with diffuse histiocytic, diffuse undifferentiated and lymphoblastic lymphomas or true histiocytic neoplasms. Twenty-six were treated with doxorubicin, cyclophosphamide, vincristine and prednisone (ACOP). The overall complete remission rate was 73%, 83% for stage I and II disease and 62% for stages III and IV. Kaplan-Meier analysis shows 49% surviving at a median follow up time of 23 months (range 1-108 months) with 11 of the 13 survivors continuously disease free. Toxicity was not severe except for one treatment-related death. Most were treated as outpatients. Patients 70 years of age or older were treated less intensively and only 3 of 14 survive. We conclude that treatment with ACOP is simple and effective in the management of high grade nonHodgkin's lymphoma. Currently our protocol includes the same agents, but at higher dosage, with the addition of methotrexate; we believe this should be tested against the recent more intensive, multiagent alternating regimens in a prospective, randomised clinical trial.

Amelioration of cytotoxic-induced emesis with high-dose metoclopramide, dexamethasone and lorazepam.

A double-blind randomised controlled trial comparing the antiemetic effects of sublingual lorazepam combined with high-dose, short course metoclopramide (3 mg/kg) infused twice 3 h apart with or without i.v. dexamethasone is reported. Sixty patients receiving a total of 209 cycles of potentially severely emetic cytotoxic chemotherapy were randomised to receive one or other antiemetic regimen. In those receiving platinum-based chemotherapy the addition of dexamethasone was associated with an improvement in freedom from nausea (P less than 0.01) and freedom from vomiting (P less than 0.05). In the non-platinum-based chemotherapy group the addition of dexamethasone led to a reduction in the duration and severity of nausea, and duration of vomiting (P less than 0.05 in each case). Both antiemetic regimens were well tolerated with a low incidence of adverse effects and could be administered easily in an outpatient setting.

Ontogeny of gastric mucosal permeability responses to luminal H+ and bile salt in the rat.

Gastric mucosal responses to intraluminal instillation of acid (10, 50, and 150 mM HCl) and acidified solutions of sodium taurocholate (10 mM) were measured in rats between 5 and 60 days after birth. Net loss of H+ and gain of Na+, K+, and protein into the gastric lumen remained low and stable up to 25 days after birth. After that there were dose-dependent increases in H+ loss and Na+ and K+ appearance in the gastric lumen. Luminal protein appearance did not change with any concentration of acid tested in any of the ages examined. Gastric instillation of sodium taurocholate resulted in an increase in the rate of H+ loss as well as Na+ and K+ appearance in neonatal rats after 12-14 days. Protein appeared in the recovered gastric instillate and increased in parallel with Na+ and K+. In response to bile salt treatment, ulcers were only evident after 35 days of age. Injection of 8-day-old rats with corticosterone acetate (250 mg/kg) did not affect the ionic fluxes or protein output in response to acid alone or acidified bile salt solutions. These studies indicate that intragastric acid loads did not increase the ionic permeability of the gastric mucosa until 25 days after birth. The permeability changes occur earlier (day 12-14) if sodium taurocholate is added to the acid instillate. Prior to that time the mucosal permeability characteristics of the neonatal rat stomach are not altered by instillation of either acid loads alone or bile salt solutions.(ABSTRACT TRUNCATED AT 250 WORDS)