Phase II study of prolonged ambulatory infusion carboplatin and oral etoposide for patients progressing through hormonal therapy for prostate cancer

Abstract
Aim :  To develop a well-tolerated outpatient chemotherapy regimen for hormone-insensitive prostate cancer.
Method :  Forty patients received carboplatin 20 mg/m² by continuous ambulatory infusion with oral etoposide 50 mg/day for 21 days repeated every 6 weeks.
Results :  Four patients had a partial response and 16 patients had stable disease. Two of the partial responders and three additional patients recorded falls in prostate specific antigen of 50% or more. The median freedom from progression was 24 weeks and median survival 32 weeks. Twenty-four of 31 patients had decreasing pain scores and 20 of 34 patients recorded improved quality of life with at least one cycle of treatment. The main toxicity occurred in seven patients with World Health Organization (WHO) grade 4 neutropenia and in four patients with WHO grade 3 neutropenia. Only one patient developed febrile neutropenia. Six patients had grade 3 anaemia and three patients had grade 3 thrombocytopenia. Two patients reported grade 3 lethargy whereas 11 patients had grade 2 lethargy.
Conclusion :  This was a well-tolerated regimen that improved symptomatic control of hormone-insensitive prostate cancer. (Intern Med J 2005; 35: 405–408)     

Concurrent chemoradiation alone with curative intent for limited-disease small-cell esophageal cancer in nine Japanese patients

Small-cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. In this retrospective study, we report clinical outcomes of limited-disease small-cell carcinoma of the esophagus from the analysis of nine patients. Between 2003 and 2006, nine consecutive patients with small-cell carcinoma of the esophagus were treated in our single institution, representing 2.8% of all esophageal malignancies treated with curative concurrent chemoradiation during this period. All the patients received four cycles of etoposide (100 mg/m², days 1–3), combined with cisplatin (80 mg/m², day 1), plus radiation therapy (50 Gy in daily doses of 2 Gy, 5 days/week). At the time of analysis, the median follow-up time was 10.8 months (range: 4.2–42.8 months) and 21.8 months in five living patients (56%). Of all the nine patients, five patients (56%) had a complete response, and the actuarial 3-year overall survival rate was 55.6%. This regimen resulted in a favorable 3-year survival rate. We conclude that the optimum treatment seems to be the same as for small-cell carcinomas of the lung, that is, a multidrug combination chemotherapy regimen used with concurrent radiation.     

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Objectives:  Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.
Methods:  The induction chemotherapy consisted of 2-CdA 5 mg/m², Ara-C 2 g/m², MIT 10 mg/m², and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA.
Results:  One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS.
Conclusions:  We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.     

Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only treatment of proven long-term efficacy in chronic myeloid leukaemia (CML), although high non-relapse mortality (NRM) observed after conventional myeloablative conditioning limits its applicability. This phase II trial evaluated the efficacy and toxicity of a new preparative regimen consisting of treosulfan 3 × 14 g/m² and fludarabine 5 × 30 mg/m², in patients with CML in chronic phase. Among the 40 patients included, 18 received alloHSCT from a sibling and 22 from an unrelated donor. All patients engrafted with 92·5% of cases achieving complete donor chimaerism by day +100. All but one patient had achieved complete cytogenetic remission on day +100. Grade III or IV non-haematological toxicities included: neutropenic fever (10%), nausea/vomiting (10%), elevated liver enzymes (5%) and infection (2·5%). The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 22·5% and extensive chronic GVHD, 14%. The 2-year probability of overall survival, leukaemia-free survival and NRM was 85%, 82·5% and 15% respectively. At 1 year post-transplant, 85% of survivors had a Karnofsky index of 100%. We concluded that treosulfan and fludarabine conditioning is a low-toxicity regimen with high anti-leukaemic potential that seems feasible in CML patients referred for alloHSCT.     

Adjuvant chemotherapy for non-metastatic osteosarcorna of the extremities in two New Zealand cancer centres

Background : Adjuvant chemotherapy significantly improves survival of patients with non-metastatic osteosarcoma but most of the data come from trials conducted in major international cancer centres.
Aim : To review the efficacy and toxicity of an adjuvant chemotherapy regimen used in two regional cancer centres in New Zealand.
Methods : Retrospective review of patients treated for non-metastatic high-grade osteosarcoma of the extremities. The regimen (POMA) consists of high-dose methotrexate 8 g/m² and vincristine 1.5 mg/m² (maximum 2 mg) on days 1 and 8 followed by folinic acid then doxorubicin 50 mg/m² and cisplatin 100 mg/m² on day 15. This cycle was repeated every 35 days. Following amputation patients received six cycles while in selected patients two cycles were planned prior to limb salvage surgery followed by a further four cycles. Actuarial survival was calculated using the Kaplan-Meier method.
Results : Twenty patients were treated with POMA between 1986 and 1993. Amputation was performed in 16 patients and limb-salvage surgery in four. Sixteen patients (80%) remain alive with no evidence of disease at a median follow-up of 40 months. Thirteen patients (65%) have been continuously disease-free. Actuarial survival at five years is 70%. Seven patients relapsed, six in lungs, of whom four underwent pulmonary metastasectomy; three of these remain free of disease 31, 35 and 40 months later. There was no local relapse. The toxicity of POMA is significant but tolerable.
Conclusion : The results obtained at two regional cancer centres in New Zealand using POMA compare favourably to those achieved in clinical trials performed at major international cancer centres.     

Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma

This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m² on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m²) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m² and bortezomib 1·3 mg/m². The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD ( n  = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD ( P  < 0·05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.     

Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma

Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma. Twenty-four patients were enrolled. Non-Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose-limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m² on days 1–3, bortezomib 1·3 mg/m² on days 1, 4, 8, 11, with rituximab 375 mg/m² on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4–30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.     

Partial splenic embolization in children with hereditary spherocytosis

Objectives:  Although total splenectomy is able to reduce clinical symptoms in patients with hereditary spherocytosis (HS), splenectomized patients are at risk to develop overwhelming bacterial infections and, to a lesser extent, thromboembolic complications. In contrast, partial splenectomy or partial splenic embolization (PSE) may also decrease the rate of hemolytic complications while maintaining residual splenic function. The aim of this study was to investigate the benefit of PSE in children with moderate to severe HS.
Patients and methods:  We performed PSE via retrograde transfemoral access in eight children (four female, four male) with moderate to severe HS at a median age of 8 yr. HS-related complications before PSE included gallstones in six and aplastic crises in four children. One patient was transfusion-dependent.
Results:  No acute side effects were seen during or after PSE. Median hemoglobin increased significantly from levels between 7.5 g/dL and 11.65 g/dL before PSE to levels between 8.4 g/dL and 13.35 g/dL after PSE ( P  = 0.012). Median splenic sizes before PSE ranged from 9.7 cm/m² to 19.0 cm/m² and significantly decreased to values between 4.4 cm/m² and 15.65 cm/m² during follow-up ( P  = 0.012).
Conclusions:  PSE appears to be a safe, effective and feasible treatment option for the management of children with moderate to severe HS.     

IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial

A phase II trial was designed to explore the potential feasibility and efficacy of a reinduction therapy consisting of fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor (G-CSF) for acute myelogenous leukaemia (AML) patients with poor prognosis.
Twenty-three patients aged 1.2–17.5 years with refractory ( n  = 3), relapsed ( n  = 19) or secondary ( n  = 1) AML were treated with the IDA-FLAG regimen, a combination therapy of idarubicin (days 2–4, 12 mg/m²/d), fludarabine (days 1–4, 30 mg/m²/d), cytarabine (days 1–4, 2000 mg/m²/d) and G-CSF (day 0 up to ANC > 1 × 10⁹/l, 400 μg/m²/d). They received a total of 37 courses of IDA-FLAG and/or FLAG (IDA-FLAG without idarubicin). 17/23 patients achieved a complete remission (CR) with a median duration of 13.5 months (1–39 months), one patient showed a partial remission, and five were nonresponders while in CR, 11 patients underwent bone marrow or PBSC (peripheral blood stem cells) transplantation. Overall, nine patients remain in continuous complete remission with a median duration of 17.5 months (9.5–39 months). The toxicity of the IDA-FLAG courses was more severe than for the FLAG courses with marked neutropenia and thrombocytopenia (for IDA-FLAG: median 22.5 and 25 d respectively; for FLAG: median 10.5 and 14 d respectively). Pulmonary infections were the main nonhaematological toxicity. One patient died in CR from invasive aspergillosis.
The IDA-FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation.     

Australian Leukaemia Study Group Myeloma II: a randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma

The Australian Leukaemia Study Group has performed a randomized trial of interferon α-2A (Roferon-A) as a co-induction agent together with intensive combination chemotherapy and as maintenance following completion of 12 cycles of induction treatment. When used as a co-induction agent, interferon-α did not improve response rates, time-to-treatment failure, or overall survival. Patients who had interferon together with intensive combination therapy (PCAB: prednisone 60 mg/m² days 1–5, cyclophosphamide 600 mg/m² day 1, BCNU 30 mg/m² day 1, doxorubicin 30 mg/m² day 1, repeated every 28 d for a total of 12 cycles) had more leucocyte and granulocyte toxicity and received a lower dose intensive of cytotoxic drugs than those patients who received PCAB without interferon.   There was a trend towards prolongation of plateau phase which did not reach significance. Interferon, however, did improve the survival of patients who achieved plateau; for those patients interferon was associated with a 33% decrease in the rate of death after adjusting for initial beta-2 microglobulin level.     

TRP64ARG polymorphism of the beta 3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle

Aim: We performed a case–control study to assess the association between obesity risk and the Trp64Arg polymorphism of the β₃-adrenergic receptor gene.
Methods: Obese subjects [n = 159; body mass index (BMI) > 30 kg/m²] and controls (n = 154; BMI < 25 kg/m²) were compared using multivariable logistic regression to control for potential confounders.
Results: A higher obesity risk (adjusted OR: 2.98; 95% CI: 1.00–8.56; p = 0.05) was associated with the Trp64Arg polymorphism among sedentary, but not among more active people.
Conclusions: Our results suggest that the TRP64ARG polymorphism of the ADRB3 seems to be a risk factor for obesity that is dependent on a sedentary lifestyle.     

Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease

Twenty-six patients with relapsed or refractory Hodgkin's disease (HD) were treated with an intensive salvage regimen combining ifosfamide (3000 mg/m²/d, days 1–4 through continuous intravenous infusion) and vinorelbine (25 mg/m², i.v. days 1 and 5) with mesna uroprotection and G-CSF support. Courses were given at 3-week intervals.
Ten patients achieved a complete and 10 patients a partial response, yielding an overall response rate of 77%. The main toxic effect was neutropenia and the combination was well tolerated.     

Identification of ''short-lived'' and ''long-lived'' patients at presentation of idiopathic myelofibrosis

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m² and rHUG-CSF 150 μg/m² daily. This regimen was well tolerated with no major adverse events reported. More than 2 × 10⁶/kg CD34⁺ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0–25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score ≥1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization ( P  =0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.     

A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity

We studied the pharmacokinetics and toxicity of 220 mg/m² melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m², total body clearance 313 ml/min/m², elimination half-life 46 min) were the same as those of 140 or 200 mg/m² melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia <25 × 10⁹/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.     

Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma

High-quality response to multiple myeloma (MM) therapy can be predictive for improved outcomes. Novel agents may improve the depth of responses and therefore prolong survival. We report on the extended follow-up of a phase II study in frontline MM of bortezomib alone and in combination with dexamethasone. Forty-nine previously untreated, symptomatic MM patients received bortezomib 1·3 mg/m², days 1, 4, 8, 11, for up to six 3-week cycles. High-dose dexamethasone was added for patients not reaching either a partial response after cycle 2 or a complete response (CR) after cycle 4. The overall response rate in 48 evaluable patients was 90%, with 42% achieving at least a very good partial response, of which 19% were CR/near CR. Thirty-six patients received high-dose dexamethasone with 28 (77%) showing improved response. Twenty-seven patients have undergone successful stem-cell transplantation (SCT). After median follow-up of 49 months, 15 patients have died; median overall survival has still not been reached, with an estimated survival at 4 years of 67%. Overall survival with and without SCT was not different ( P  = 0·54). Grade 3/4 adverse events included neutropenia (10%), sensory neuropathy (6% grade 3), neuropathic pain (4% grade 3), and diarrhoea (4% grade 3). Bortezomib ± dexamethasone is an effective and well-tolerated induction regimen for the frontline treatment of MM.     

A single institutional non-randomized retrospective comparison between definitive chemoradiotherapy and radical surgery in 82 Japanese patients with resectable esophageal squamous cell carcinoma

SUMMARY.  This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus. Between June 2000 and May 2005, 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery. The patients in the chemoradiotherapy (CRT) group received 2–4 cycles of 5-fluorouracil (1000 mg/m²/day, day 1–4, continuous) combined with cisplatin (75 mg/m², day 1, bolus) plus 50.4 Gy of radiation, while those in the surgery group were treated by an esophagectomy with radical node dissection. Eighteen surgical patients received postoperative chemotherapy. The baseline clinical TNM stage was similar between the two groups. With a median follow-up period of 36 months (range: 23–84 months) with 47 survivors (57%), the 3-year overall survival rates ( P = 0.22) and disease-free survival rates ( P = 0.16) were 48% and 44% in the chemoradiotherapy group versus 65% and 59% in the surgery group, and lacked statistical significance. This non-randomized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients. There is a trend toward improved survival with surgery versus definitive CRT.     

Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial: an interim report

Objective:  The Veterans Affairs Diabetes Trial (VADT) will assess the effect of intensive (INT) vs improved standard (STD) glycaemic control on major cardiovascular (CV) events, treating other risk factors equally in both arms. Four-year results of main metabolic parameters are presented.
Research design and methods:  VADT is a 7.5 years prospective randomized study of 1791 patients, 20 centres, of men and women of age 60.5 ± 8.7 years, diagnosed for 11.5 ± 7.5 years. Their body mass index (BMI) at baseline was 31 ± 4 kg/m² and mean A1C 9.4 ± 1.5% after maximum dose of oral agents or insulin treatment. Step treatment consists of glimepiride or metformin, rosiglitazone, insulin and other agents; A1C goals are 8–9% in STD and <6% in INT. Lifestyle, blood pressure and lipids are treated uniformly in both arms.
Results:  A1C improved in both arms. INT kept median A1C <7% all years, A1C separation is 1.5–1.7%. From year 1 to 4, mean blood pressure is <129/74 mmHg, similar throughout. Median LDL-C was <97 mg/dl by year 1 and triglycerides 150 or less by 2 years. Triglycerides were lower in INT (12–16 mg/dl; p < 0.01). By 4 years, 88% are on lipid-lowering agents and 93% are on antiplatelet/anticoagulant agents. BMI is higher in INT every year (0.9–1.6 kg/m²; p < 0.01).
Conclusion:  VADT is maintaining the expected A1C in both STD and INT, and LDL-C, triglycerides and blood pressure are at target. The trial is continuing to June 2008. It will be the first long-term completed type 2 diabetes study of the role of glycaemia on CV disease with modern treatments.     

Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia

The safety and efficacy of the combination clofarabine/cyclophosphamide/etoposide were evaluated in children with advanced acute lymphoblastic leukaemia (ALL). The study enrolled 25 paediatric patients (median age 12·5 years) with either refractory ( n  = 17; 68%) or multiple relapsed ( n  = 8; 32%) ALL to receive clofarabine 40 mg/m², cyclophosphamide 400 mg/m² and etoposide 150 mg/m², daily for 5 consecutive days. No patient died from treatment-related complications. The most common adverse events were febrile neutropenia, mucositis and reversible liver toxicity; no case of liver veno-occlusive disease was reported. The overall remission rate was 56%: 13 patients (52%) achieved complete remission (CR) and one (4%) CR without platelet recovery (CRp). In seven of the 13 (54%) patients achieving CR, remissions were of sufficient duration to allow patients to receive allogeneic haematopoietic stem cell transplantation. The probability of CR/CRp was greater in the 17 patients with B cell precursor ALL than in the eight with T-ALL (76% vs. 12%, respectively, P  <   0·01). The 18-month overall survival probability was 39% and 0% in patients who did or did not respond to the treatment, respectively ( P  <   0·01). These data suggest that the clofarabine/cyclophosphamide/etoposide regimen is well tolerated and can induce clinical response in a relevant proportion of children with refractory/multiple relapsed ALL.     

Obesity: A Risk Factor for Severe Acute Biliary and Alcoholic Pancreatitis

Objective: In this study we evaluate the association between obesity and complication development in patients with a first-attack acute pancreatitis (AP), and investigate the influence of comorbid factors on this association.
Methods: Medical records of 150 patients with AP were reviewed. General data, AP etiology, admission AP prognostic criteria, and occurrence of complications were recorded. Patients were classified according to body mass index (BMI) as obese (  BMI > 25  kg/m²) and nonobese (  BMI ≤ 25  kg/m²).
Results: Prevalence of obesity was 57%. Thirty-eight percent of the obese patients developed complications as compared with 21% of the nonobese (  RR = 1.74  ; 95% CI, 1–2.9). The risk for severe AP increased according to the degree of obesity. Pancreatic and peripancreatic necrosis was more common in obese patients (17.6% vs 6%), as was the incidence of infectious complications. The risk for severe AP was highest in obese patients with either alcoholic (  RR = 5.3  ; 95% CI, 1.2–23) or biliary etiology (  RR = 5.2  , 95% CI, 1–26).
Conclusion: Obesity may predispose to a complicated course of AP, especially if it is secondary to alcohol or gallstones. Further studies are needed to establish the precise prognostic value of obesity in AP, as well as the pathogenic mechanisms involved in the process.     

长春瑞滨与铂类联合治疗70岁以上老年人非小细胞肺癌的临床观察

目的 研究长春瑞滨与铂类联合治疗70岁以上非小细胞肺癌患者的疗效和毒副反应.方法 老年肺癌患者共入选100例.化疗组50例,采用长春瑞滨25 mg/m2第1天和第5天,顺铂60～70mg/m2或卡铂250 mg/m2第2天,每4周为1个周期,连用2～4周期.对照组50例,为同期70岁以上患者,资料完整且未做治疗.结果 治疗组45例可评价疗效,部分缓解16例,有效率35.6%,1年生存率37.8%,中位生存期9.8个月;对照组中位生存期4.0个月.治疗组50例均可评价毒副反应,世界卫生组织(WHO)毒副反应标准Ⅲ度白细胞、中性白细胞、贫血发生率分别为38.0%、52.0%和2.2%,IV度中性粒细胞减少发生率35.5%.WHO毒副反应标准Ⅲ度非血液学毒性乏力、呕吐和便秘发生率分别为22.0%、14.0%和8.0%,因毒性反应终止治疗共5例.结论 长春瑞滨与铂类联合治疗高龄非小细胞肺癌有效且毒副反应可耐受.疗效稳定的患者也可从化疗受益.