Randomized Phase II Trial Comparing Carboplatin Plus Weekly Paclitaxel and Docetaxel Alone in Elderly Patients With Advanced Non‐Small Cell Lung Cancer: North Japan Lung Cancer Group Trial 0801

Background.

Standard first-line chemotherapy for elderly non-small cell lung cancer (NSCLC) patients has been monotherapy with vinorelbine or gemcitabine. Docetaxel has also been considered as an alternative option for the elderly population in Japan. We have previously demonstrated the high efficacy of carboplatin plus weekly paclitaxel for elderly NSCLC patients. Consequently, we conducted a randomized phase II study to select the proper regimen for a future phase III trial.

Methods.

Eligible patients were aged 70 years or older with newly diagnosed advanced NSCLC. Patients were randomly assigned either to a combination of carboplatin (area under the curve: 6 mg/mL per minute) with weekly paclitaxel (70 mg/m²) (CP regimen) or to single-agent docetaxel (60 mg/m²). The primary endpoint of this study was objective response rate. Secondary endpoints were progression-free survival, overall survival, and toxicity profile.

Results.

Among 83 eligible patients (41 to CP, 42 to docetaxel), the objective response rates were 54% (95% confidence interval: 39%–69%) and 24% (95% confidence interval: 11%–37%) and median progression-free survival was 6.6 months and 3.5 months in the CP arm and the docetaxel arm, respectively. Severe neutropenia, febrile neutropenia, and nausea were significantly frequent in the docetaxel arm, whereas toxicities in the CP arm were generally moderate. One treatment-related death was observed in the docetaxel arm.

Conclusion.

The CP regimen achieved higher activity with less toxicity than single-agent docetaxel. Considering the results of this phase II trial and the IFCT-0501 trial, we have selected the CP regimen for a future phase III trial in elderly patients with advanced NSCLC.     

A Randomized Phase II Study of Carboplatin With Weekly or Every‐3‐Week Nanoparticle Albumin‐Bound Paclitaxel (Abraxane) in Patients With Extensive‐Stage Small Cell Lung Cancer

Background.

Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules.

Methods.

This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m² on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m² on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles.

Results.

Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual.

Conclusion.

Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments.     

卡铂为主化疗同步结合放射治疗非小细胞肺癌

[目的]观察卡铂为主的化疗方案同步结合放射治疗非小细胞肺癌(NSCLC)的临床疗效.[方法]选择NSCLC患者100例随机进入放化疗同步治疗组和放疗化疗序贯治疗组,两组病例均给予常规放疗,同步组放疗开始的1、4、8、12周给予化疗(卡铂加氟尿嘧啶);序贯组在放射治疗结束后给予4个周期的化疗(卡铂、丝裂霉素加长春新碱).[结果]同步组和序贯组的近期疗效有效率分别为82%和64%;1、3、5年生存率、中位生存期分别为76%、32%、15.7%、28个月和62%、22%、9.9%、18.6个月,两组差异有显著性(x2=4.373,P＜0.05).两组患者的毒副反应主要为可逆性骨髓抑制、放射性食管炎和放射性肺炎,两组发生率相似.[结论]卡铂为主的化疗同步结合放射治疗NSCLC效果好于放疗后化疗的序贯治疗.     

Maintenance and Consolidation Therapy in Patients with Unresectable Stage III/IV Non‐Small Cell Lung Cancer

Globally, lung cancer is the leading cause of cancer‐related mortality. Current chemotherapy combinations for the first‐line treatment of advanced disease (stage IIIB with malignant pleural effusion/stage IV) and chemoradiotherapy regimens for the treatment of unresectable locally advanced disease (stage IIIA and IIIB without malignant pleural effusion) appear to have reached an efficacy plateau. The addition of new compounds including targeted agents to standard first‐line cytotoxic doublets, administered concurrently and/or as maintenance therapy in patients who have not experienced disease progression after such treatment, has been shown to improve efficacy beyond this plateau in patients with advanced disease. However, to date, such approaches have been less successful in the treatment of patients with unresectable locally advanced stage III disease. The purpose of this review is to summarize the data from recent randomized phase III studies involving agents administered as maintenance or consolidation therapy in the treatment of unresectable stage III/IV non‐small cell lung cancer (NSCLC). A possible alternative approach to the use of cytotoxic or molecularly targeted agents in this setting is the administration of therapeutic anticancer vaccines, which are designed to stimulate a host immunological response against the tumor. Current data in relation to the potential of vaccine therapy for NSCLC are therefore also reviewed, with a particular focus on belagenpumatucel‐L and L‐BLP25 vaccines, which are currently undergoing phase III evaluation as maintenance therapies in patients with unresectable stage III/IV NSCLC who have tumor control following first‐line therapy.     

Measuring the Population Impact of Introducing Stereotactic Ablative Radiotherapy for Stage I Non‐Small Cell Lung Cancer in Canada

Background.

The Cancer Risk Management Model (CRMM) was used to estimate the health and economic impact of introducing stereotactic ablative radiotherapy (SABR) for stage I non-small cell lung cancer (NSCLC) in Canada.

Methods.

The CRMM uses Monte Carlo microsimulation representative of all Canadians. Lung cancer outputs were previously validated internally (Statistics Canada) and externally (Canadian Cancer Registry). We updated costs using the Ontario schedule of fees and benefits or the consumer price index to calculate 2013 Canadian dollars, discounted at a 3% rate. The reference model assumed that for stage I NSCLC, 75% of patients undergo surgery (lobectomy, sublobar resection, or pneumonectomy), 12.5% undergo radiotherapy (RT), and 12.5% undergo best supportive care (BSC). SABR was introduced in 2008 as an alternative to sublobar resection, RT, and BSC at rates reflective of the literature. Incremental cost effectiveness ratios (ICERs) were calculated; a willingness-to-pay threshold of $100,000 (all amounts are in Canadian dollars) per quality-adjusted life-year (QALY) was used from the health care payer perspective.

Results.

The total cost for 25,085 new cases of lung cancer in 2013 was calculated to be $608,002,599. Mean upfront costs for the 4,318 stage I cases were $7,646.98 for RT, $8,815.55 for SABR, $12,161.17 for sublobar resection, $16,266.12 for lobectomy, $22,940.59 for pneumonectomy, and $14,582.87 for BSC. SABR dominated (higher QALY, lower cost) RT, sublobar resection, and BSC. RT had lower initial costs than SABR that were offset by subsequent costs associated with recurrence. Lobectomy was cost effective when compared with SABR, with an ICER of $55,909.06.

Conclusion.

The use of SABR for NSCLC in Canada is projected to result in significant cost savings and survival gains.     

Stereotactic Radiotherapy for Stage I Small Cell Lung Cancer

Although the use of stereotactic ablative radiotherapy (SABR) for stage I small cell lung cancer is in its infancy, there are many reasons to believe that with more time and experience, it could emerge as the standard of care in inoperable patients, and perhaps even have equipoise with surgery for operable patients. Reporting of modeling studies and as much clinical data as possible are very much needed.Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy, is a burgeoning radiotherapy modality that involves precisely directing radiation to the tumor site, with increased focus on patient immobilization during treatment (including respiratory motion accountability), and, by definition, administers large doses of radiation in five or fewer treatments [1]. SABR is an excellent alternative to surgery in patients with medically inoperable non-small cell lung cancer (NSCLC), demonstrating local control rates of greater than 90%, minimal treatment morbidity, and essentially no risk of treatment-related mortality [2]. In the absence of completed phase III data and mature phase II data [3, 4] on SABR in patients with operable NSCLC, its use in these patients remains controversial. However, the successes of SABR in achieving high local tumor control and low toxicity bring forth the question of whether SABR can be a viable option in patients with stage I small cell lung cancer (SCLC), particularly those who are medically inoperable.Per the National Comprehensive Cancer Network guidelines [5], treatment for T1–2 N0 (no regional lymph node metastasis) M0 (no distant metastasis) SCLC includes lobectomy with mediastinal lymph node dissection. If nodes are pathologically negative, adjuvant chemotherapy is warranted, whereas adjuvant chemoradiation is endorsed if nodes are involved. For inoperable patients or those who refuse surgery, chemotherapy with or without radiation that is delivered in conventional fractionation is the only option listed. Thus, SABR is not currently part of management options for operable/inoperable disease, owing to the paucity of stage I SCLC data, and essentially no data on the use of radiotherapy in such situations.Randomized data have failed to demonstrate a survival benefit for surgery in SCLC. Median survival was longer in patients randomized to radiotherapy compared with surgery on the British Medical Research Council trial (10 vs. 6.5 months; p = .04), which included generally more advanced patients [6]. In the Lung Cancer Study Group 832, among 146 patients achieving a partial or complete response to chemotherapy, patients randomized to surgery did not have a survival benefit over those randomized to chemoradiation (p = .78) [7]. Three percent postoperative mortality was observed. Of note, most patients in that study were node positive and only 13% had T1–2 N0 disease. Most evidence supporting the use of surgery in SCLC has come from modestly sized retrospective studies examining surgery and chemotherapy [8, 9], in which 5-year overall survival (OS) ranged from 40% to 60%.Despite current recommendations, it is clear that relatively low levels of evidence exist for surgery in management of stage I SCLC. Thus, at many centers, it is not uncommon to forego surgery in favor of chemoradiotherapy. The gap in recommendations and clinical practice sheds light as to whether SABR is an appropriate option for these patients. Because of the absolute dearth of evidence in this realm, it is important to scrutinize data on SABR in NSCLC [10].SABR is the treatment of choice for medically inoperable NSCLC; new pooled data from discontinued phase III randomized trials now support that OS for SABR in operable patients is not inferior to that of surgery [11]. This is in keeping with high OS rates for medically operable patients reported for prospective phase II studies at interim analysis in the Japan Clinical Oncology Group (JCOG 0403) trial (76.0% at 3 years) [4] and the Radiation Therapy Oncology Group (RTOG 0618) trial (84.4% at 2 years) [3]. Furthermore, patterns-of-failure analyses for SABR in NSCLC have demonstrated that most recurrences occur distantly [12], a finding supported by seminal SABR trials [2]. Hence, surgical sampling to assess for occult nodal disease in patients with radiographically and metabolically negative lymph nodes may be of less consequence than administering systemic therapy in efforts to decrease distant (and regional) failure. This fact is especially applicable to SCLC, which presents with distant metastases more frequently than NSCLC.Outcomes of SABR have been consistently superior to those for conventional radiotherapy for early-stage NSCLC, including those from a meta-analysis that demonstrated more than double the 5-year OS [13, 14]. Thus, there is no reason to think differently for SCLC if chemoradiation is electively performed in lieu of surgery, as is done at some institutions.SABR versus surgery in SCLC (and NSCLC) is less clear cut. Given the evolving role of SABR in patients with medically operable NSCLC but the complete dearth of literature supporting SABR for patients with medically operable SCLC, it is likely too presumptive to assume equivalence in outcomes (resection is still performed if operable clinical stage I). However, specifically in medically inoperable patients with stage I SCLC, SABR with chemotherapy may be most optimal. This is a particularly important patient population, given that patients with SCLC generally present with heavier smoking histories, more advanced age, and higher medical comorbidity scores than their NSCLC counterparts and, thus, may often be found as medically inoperable. The only current recommendation for medically inoperable patients is chemoradiation, with conventionally fractionated radiation recommended simply because of the lack of available data with SABR as the radiation modality. However, as mentioned, the clear success of SABR versus conventionally fractionated radiation for early-stage NSCLC is evidence that SABR should be evaluated for stage I SCLC. It is, therefore, very possible that SABR could produce increased OS in patients with SCLC as compared with conventional radiotherapy, although this needs to be tested prospectively. Thus, continuing to perform conventional radiotherapy in patients with stage I inoperable disease, as occurs in many practices, could ultimately prove to compromise survival.In all likelihood, however, there are a few patients at many centers who have undergone SABR for stage I SCLC, and the best way to accumulate data at this point is through case reports/series until systematic reviews and meta-analyses can be performed. Although a few studies have examined SABR for SCLC and found equivalent or better outcomes compared with historical conventionally fractionated treatments, there are essentially no patients with stage I disease without stratification of outcomes based on stage [15].Based on thorough PubMed and EMBASE searches, there have been three published case series, with a total of 22 patients, examining SABR for stage I SCLC. In one report, eight patients with cT1–2 N0 M0 biopsy-proven SCLC, two of whom refused surgery, underwent SABR (48 Gy in four fractions) [16]. Six patients underwent chemotherapy before (n = 4) or after (n = 2) SABR. At median follow-up of 32 months, local control was 100% and 3-year OS was 72%, with only one patient dying of SCLC; this patient refused chemotherapy and disease recurred nodally. Another series of six patients with inoperable SCLC, from Cleveland Clinic [17], underwent chemotherapy and SABR with local control of 100%, 1-year OS of 63%, and limited toxicity (one and zero patients with grade 2 and grade ≥3 toxicities, respectively). Among three patients who died, only one died with distant failure; there were no nodal failures. This suggests that similar to experiences with early-stage NSCLC, some patients will die of comorbid conditions other than lung cancer. The final case series [18] treated eight inoperable patients with SABR (50 Gy in four fractions) and adjuvant chemotherapy per physician’s discretion. Although local control was 100%, 3-year OS was 60%, and only 37% in patients not receiving chemotherapy.The largest studied cohort is only published in abstract format—a Japanese multi-institutional pool of 64 patients with biopsy-proven stage I SCLC who were inoperable or refused surgery [19]. SABR was performed at doses of 35–60 Gy in three to eight fractions. Thirty-six patients received chemotherapy (three or four cycles). Although 3-year local control was 90%, distant metastases were seen in 26 patients and nodal metastases in 18 patients. The 3-year OS was 62%.There are several points to be gleaned from these limited data. First, local control with SABR is, in many cases, close to 100%, which means that there may be little extrapolation of this parameter needed between early-stage NSCLC and SCLC. Second, whereas 5-year OS after surgery and chemotherapy ranges from 40% to 60% in aforementioned retrospective data, 3-year OS with SABR and chemotherapy has ranged from 60% to 72%, despite most patients who were treated with SABR/chemotherapy being medically inoperable because of greater comorbidities. Third, just as chemotherapy has been shown to significantly improve survival in patients with more advanced SCLC [20], chemotherapy should be considered for patients with stage I SCLC, as well, given the limited data on patients not receiving chemotherapy tending to show poorer outcomes.These incomplete data create an interesting conundrum: albeit low sample sizes, because of the aforementioned comparable survivals, is there a chance that SABR/chemotherapy could also be comparable to surgery/chemotherapy in patients with operable stage I SCLC who tend not to die of comorbidities? Although the field is a long way from testing this hypothesis, population modeling studies (e.g., Markov modeling or Cancer Intervention and Surveillance Modeling Network) can be compelling ways to test these notions and estimate survivals in large groups of patients with stage I SCLC who are undergoing SABR with chemotherapy, in efforts to provide estimates on outcomes, given the strikingly obvious lack of existing data.There are several questions of interest that can change clinical practice in these patients if more data are elucidated. What is the optimal timing of chemotherapy with SABR? Published studies [16–18] have used neoadjuvant, concurrent, and adjuvant chemotherapy. Furthermore, what is the role of prophylactic cranial irradiation (PCI) in these patients, done routinely in both limited- and extensive-stage SCLC owing to OS benefits? Although no data have demonstrated intracranial failure, some institutions have used PCI [17] and others have not [16]. In a study examining the role of PCI in patients with surgically treated SCLC, the authors only noted two of 32 patients (6.25%) developed brain metastases, provided complete surgical resection was performed [21]. Additionally, receipt of induction or adjuvant chemotherapy did not affect the risk of brain metastasis, a notion worth considering in light of previously published results. Although it is problematic to assume that the numbers for complete surgical resection would be equivalent to those of SABR, the incidence can be used as a benchmark on which to argue for (or against) PCI in these patients.Although stage I SCLC is rare overall, the recent approval of low-dose computed tomography screening by Medicare will certainly bring forth more cases of stage I SCLC, given that 8% of detected cancers in the National Lung Cancer Screening Trial were SCLC [22–25]. Although the use of SABR for stage I SCLC is in its infancy, there are many reasons to believe that with more time and experience, it could emerge as the standard of care in inoperable patients, similar to early-stage NSCLC, and perhaps even have equipoise with surgery for operable patients. Reporting of modeling studies and as much clinical data as possible are very much needed.     

Phase I/II Study of Cisplatin plus Nab‐Paclitaxel with Concurrent Thoracic Radiotherapy for Patients with Locally Advanced Non‐Small Cell Lung Cancer

Lessons Learned

• The combination of cisplatin plus nab‐paclitaxel with concurrent thoracic radiotherapy in unresectable stage III non‐small cell lung cancer is a promising therapeutic strategy.
• Further investigation is warranted.

BackgroundWe conducted a phase I/II trial of cisplatin plus nab‐paclitaxel with concurrent thoracic radiotherapy for locally advanced non‐small cell lung cancer (NSCLC) to determine the recommended dose (RD) of nab‐paclitaxel and to evaluate the safety and efficacy of this regimen.MethodsIn the phase I study, escalating doses of weekly nab‐paclitaxel were administered together with cisplatin at 75 mg/m² every 3 weeks and concurrent radiotherapy. In the phase II study, nab‐paclitaxel was administered at the RD.ResultsIn the phase I study, whereas no dose‐limiting toxicity (DLT) was observed with nab‐paclitaxel at 50 or 60 mg/m², one of six patients experienced DLT (esophagitis of grade 3) at 70 mg/m², determined as the RD. Twenty‐four patients at RD were evaluable for safety and efficacy in phase II. Common toxicities included esophagitis (87.5%) and leukopenia (79.2%). Pneumonitis and treatment‐related deaths were not observed, but 20 patients (83.3%) experienced radiation pneumonitis, with one case of grade 3 and four of grade 2, after completion of concurrent chemoradiotherapy. The 2‐year overall survival and progression‐free survival rates were 73.9% and 56.5% (95% confidence interval [CI], 34.3%–74.7%), respectively.ConclusionConcurrent chemoradiation with nab‐paclitaxel at 70 mg/m² and cisplatin at 75 mg/m² every 3 weeks showed encouraging feasibility and activity for locally advanced NSCLC.     

紫杉醇加顺铂同步放化疗治疗局部晚期非小细胞肺癌的临床观察

目的:探讨紫杉醇加顺铂同步放化疗治疗局部晚期非小细胞肺癌(NSCLC)的疗效和毒副反应。方法:32例患者行常规分割放疗40Gy,针对局部病灶行三维适形放疗(3DCRT)加量至中位总剂量达70Gy/35次。化疗方案为紫杉醇135mg/m2静脉滴注第1天,顺铂20mg/m2静脉滴注,第1天～4天。结果:全组32例均可评价疗效,总有效率(CR+PR)为71.9%。中位缓解期为8.6个月,中位生存期为15.2个月,1年、2年的生存率分别为68.8%和46.9%。主要毒性反应为白细胞减少,Ⅲ度16例(50.0%),Ⅳ度3例(9.7%)。急性放射性肺炎1级～2级13例(40.6%);急性放射性食管炎1级～2级17例(53.1%),3级2例(6.3%)。结论:紫杉醇加顺铂同步放化疗治疗局部晚期NSCLC局控率较高,骨髓毒副反应较明显,急性放射性损伤在大多数患者尚可耐受。     

紫杉醇联合卡铂每周方案新辅助化疗治疗非小细胞肺癌

[目的]探讨紫杉醇联合卡铂每周方案新辅助化疗治疗非小细胞肺癌的疗效和不良反应.[方法]54例非小细胞肺癌入组,按随机原则分组,试验组29例术前新辅助化疗,对照组25例直接手术.术前化疗,紫杉醇80mg/m2每周给予,共9次,卡铂AUC 6每3周给予,共3次,化疗结束后2～6周手术,行肺叶切除及纵隔淋巴结清扫.化疗前后影像学检查测量肿块大小,术后行病理检查.[结果]试验组29例患者均完成新辅助化疗,总有效率55.2％(16/29).临床完全缓解4例,其中2例达病理完全缓解,部分缓解12例,稳定13例,无疾病进展.不良反应主要包括3～4度中性粒细胞减少11例(37.9％),3度恶心1例(3.4％).手术切除率为89.7％(26/29),手术并发症主要有肺部感染10.3％(3/29)、心律失常6.9％(2/29)、乳糜胸3.4％(1/29)、支气管残端瘘3.4％(1/29)等.中位随访42个月,3年总生存率为41.4％,明显优于对照组(24.0％).[结论]紫杉醇联合卡铂每周方案具有较好的耐受性,不增加术后并发症及死亡率,具有较高的有效率.     

Benefit of Concurrent Versus Sequential Chemoradiotherapy in Elderly Patients With Stage III Non-Small Cell Lung Cancer

IntroductionLung cancer is the largest cause of cancer-related deaths worldwide. Eighty-five percent of patients is diagnosed with non-small cell lung cancer (NSCLC). Almost a third of patients is aged over 75, but this group is poorly represented in clinical trials. This study compares the effects of therapy in non-operable stage III NSCLC in elderly patients compared to their younger counterparts.Patients and MethodsThis is a retrospective cohort study. Patients are divided into three groups; patients younger than 65, patients aged between 65 and 75 and patients of 75 years or older. Concurrent chemoradiotherapy is compared to sequential chemoradiotherapy using Cox regression analysis. The primary outcome is survival. A sub analysis is performed for the presence of toxicity using logistic regression.ResultsSeven hundred and fifty patients were diagnosed with stage III NSCLC and treated with concurrent (442) or sequential (308) chemoradiotherapy. Concurrent chemoradiotherapy provides a decreased HR of death of 0.72 (0.560-0.85) compared to sequential chemoradiotherapy, even when corrected for age. Elderly patients receiving concurrent chemoradiotherapy do not have a significantly larger risk of toxicity.ConclusionsPatients of all ages with stage III NSCLC benefit from concurrent chemoradiotherapy compared to sequential chemoradiotherapy. Age is not a deciding factor in this prospect, nor do the patients experience more severe toxicity than their younger counterparts.     

Concurrent Cisplatin-etoposide Chemotherapy plus Thoracic Radiotherapy for Limited-stage Small Cell Lung Cancer

A recent approach in the treatment of limited-stage small celllung cancer (LDSCLC) has involved a combined modality of chemotherapyand chest irradiation. In using the modality, the study of schedulingmethods for combining chemotherapy and radiotherapy should leadto other trials of combined modalities against LDSCLC sinceit is the most basic issue to be evaluated. We have thus conducteda multicenter phase II trial of concurrent cisplatin-etoposide(PVP) chemotherapy and radiotherapy for LDSCLC to determinethe effects of the concurrent administration of a PVP regimenand chest irradiation on response rate, relapse, survival andtreatment toxicity. The chemotherapy regimen consisted of afour-week cycle: cisplatin (80 mg/m², given intravenously onday 1) and etoposide (100 mg/m2, given intravenously on days1–3). This cycle was given four to six times within sixmonths. Chest irradiation to the primary tumors at both thehili and the mediastinum was administered in standard fractionson days 2–12 in the first cycle of chemotherapy and ondays 29–47 in the second cycle, with a total dose of 40–50Gy. Prophylactic cranial irradiation was performed among completeremission (CR) or good partial remission (PR) patients aftercompletion of the concurrent therapy. A total of 66 patientswere entered into the trial and 59 were evaluated. The concurrenttherapy induced an overall response rate of 94.9% in 59 patients:24 patients, 40.7% CR, 32 patients, 54.2% PR. The median responseduration was 8.7 months, and the median survival time for alleligible patients was 14.8 months. The percentage of patientswith two-year survival periods was 20. A local relapse withinthe irradiated area was seen in only 22% of relapsed patients.Brain metastases occurred in 24% of patients. Four of 32 patientstreated with prophylactic cranial irradiation had brain metastases.Toxic effects, chiefly grades 3 and 4 leukopenia, as establishedby the World Health Organization, were detected in all treatedpatients. Other toxicities, including radiation-induced esophagitisand pneumonitis, were deemed almost acceptable. We concludedconcurrent treatment of a PVP regimen with chest irradiationto be a feasible and beneficial therapy with an efficacy compatibleto that of other published reports. The outcome of this protocolwarrants further investigation to determine the optimal typeof schedule for concurrent chemoradiotherapy against LDSCLC.