Inoperable Stage IIIA Research Articles

Effects of Neoadjuvant Therapy After the Initial Assessment of Operability in Patients with Borderline Operable and Inoperable Stage IIIA Non-small Lung Cancer.

Introduction:Lung cancer is a neoplasm with the highest mortality rate in the world. The role of neoadjuvant therapy in patients with initially assessed borderline operable or inoperable lung cancer is to improve survival by downstaging the tumor and allowing surgical resection, as well as the potential treatment of micrometastatic disease.Aim:Establishing the justification and efficacy of neoadjuvant therapy after the initial assessment of operability in patients with borderline operable and inoperable histopathologically verified stage IIIA non-small cell lung cancer.Methods:The retrospective study included 65 patients with initially assessed stage IIIA lung cancer, who underwent neoadjuvant therapy. After the cycles of neoadjuvant therapy, 19 patients who achieved the regression of the tumor underwent surgery. We analyzed the histological type of the tumor, extent, and prevalence of surgical resection, the status of regional lymph nodes, and the achieved R status.Results:Of the total number of patients who underwent neoadjuvant therapy, after reevaluation of the disease, 19 patients (19/65, 29.23% of cases) achieved a clinical response, i.e. tumor downstaging. Of 19 patients who underwent surgery, 16 patients underwent surgical resection, while three patients underwent surgical exploration. The largest number of patients had N0 and N1 status (six patients each). R0 status was achieved in 14 patients (14/16, 87.5% of cases), while R1 in the remaining two. One patient had a fatal outcome.Conclusion:Neoadjuvant therapy plays an important role in the treatment of initially assessed borderline operable or inoperable lung cancers. By downstaging the tumor, it allows surgical resection and potential treatment of micrometastatic disease.

Modified ketogenic diet in solid tumors: A Veteran Affairs Pittsburgh Healthcare System case series.

e14217 Background: Cancers prefer glucose due to mitochondrial dysfunction. Ketogenic diets fuel normal cells while starving cancer. Sparse data exists on ketogenic diets in solid tumors. Methods: Studied 5 advanced solid tumor patients on a modified ketogenic diet plus standard of care chemotherapy. Daily carbohydrate limited to 20-40 grams, no sweets or starch. Histories and clinical courses are presented. Results: Case 1: 70 year old male, medically inoperable Stage IIIA poorly differentiated squamous cell lung cancer and non-hodgkins lymphoma. Treated with radiation and paclitaxel/carboplatin. After 5 months, lung cancer relapsed in a neck mass, treated with chemoradiation plus the diet. At 46 months, scans and blood counts were normal. Case 2: 42 year old, 417 lb. male diabetic stage IV colon cancer, spread to lungs and liver. Progressed on 5FU/bevacizumab/oxaliplatin, irinotecan, tipiracil/trifluridine, regorafenib but responded to 5FU/irinotecan rechallenge plus liver chemoembolization. Dieted, mild ketosis but lost 64 lbs, stable disease at 6.5 years. Case 3: 42 year old male, Stage III BRAF V600 E melanoma, Vemurafenib intolerant. Bulky axillary nodes resected plus diet for 3 years. Complete remission at 7 yrs 9 months. Case 4: 57 year old male, medically inoperable liver cancer, normal AFP values and normal scans after 5 months of sorafenib. AFP later increased to 690 ng/ml. Advised to change treatment but he refused and started the ketogenic diet with the sorafenib. After 5 months, AFP improved to 445 ng/ml. Sorafenib and diet interrupted for 3 months, AFP rose to 1017. At 7 yrs, 4 months, back on sorafenib and diet, AFP 1520 mg/ml, negative scans. Case 5: 49 year old male, aggressive digital papillary skin adenocarcinoma, multi-organ metastases. Had side-effects with many chemotherapies (paclitaxel/bevacizumab/carboplatin, sorafenib, gemcitabine, oxaliplatin/5FU, cyclophosphamide) Stable disease on diet despite multiple therapy changes. At 34 months, he was off the diet, tumors grew plus new brain lesions (resected). Alive on atezolizumab at 36 months. Conclusions: Ketogenic diets in human solid tumors seem well tolerated and may improve response and survival after standard therapy.

Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB and IIIA Non-small Cell Lung Cancer

Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB and IIIA Non-small Cell Lung Cancer

PACIFIC trial: new perspectives for immunotherapy in lung cancer

Lung cancer still represents the most frequent cause of cancer-related mortality worldwide and 85% of all lung neoplastic disease are classified as non-small-cell lung cancer (NSCLC) (1); approximately one third of NSCLC are locally advanced disease at diagnosis (2). Actually, the standard-of-care for unresectable or inoperable stage IIIA and IIIB disease for patients with good performance status consists of platinum-based doublet chemotherapy (CT) concurrent with 60 Gy of radiotherapy (RT) administered daily over 6 weeks followed by possible further two cycles of consolidative CT (2). The supportive evidence for the use of concomitant chemoradiotherapy (CT/RT) is rooted in many clinical trials, with evidence of better results of concurrent CT/RT compared to either modality of administration of CT and RT, alone or sequential (3). The 5-year overall survival (OS) rate is 15–35% for stage IIIA and 5–10% for stage IIIB (4). Although survival outcomes are poor, notable is that a subset of the patients are potentially curable.

Continuous Intravenous Infusion Recombinant Human Endostatin Combined with Concurrent Chemoradiation Therapy in Unresectable Stage III Non–small Lung Cancer—Results of a Multicenter Phase 2 Study (NCT01733589)

Concurrent radiotherapy is the standard treatment of unresectable stage III non-small lung cancer (NSCLC) but with unsatisfied results. Tumor angiogenesis is one of the most important targets for novel agents’ exploration. Recombinant human endostatin, an angiogenesis blocker, has been indicated to normalize the tumor vasculature to make it more efficient for oxygen delivery, thereby provide a window of opportunity for enhanced sensitivity to radiation treatment. To evaluate the efficacy and safety of the addition of continuous intravenous infusion of recombinant human endostatin to concurrent chemoradiotherapy in inoperable stage III NSCLC, we designed this phase 2 study. This trial was approved by the institutional ethics committees of the four participating institutions. The study was registered on the website of ClinicalTrials.gov (NCT01733589).The eligible patients should meet the following criteria before treatment: untreated histologically or cytologically diagnosed NSCLC, inoperable stage IIIA or IIIB according to AJCC seventh staging system, performance score of 0 to 1, blood coagulation is normal. Patients with preexisting bleeding diatheses were excluded. All of the enrolled patients received thoracic radiation with dose of 60-66 Gy, continuous intravenous infusion of recombinant human endostain (7.5 mg/m2/24 h, 120 h, d-6-d-2, d8-d12, d22-d26, d36-d40, from the beginning of radiotherapy) and two cycles of etoposide (50 mg/m2, d1-d5, d29-d33) plus cisplatin (50 mg/m2, d1, d8, d29, d36). The primary endpoint was progression free survival (PFS) and the secondary endpoints were response, overall survival (OS), local regional free survival (LRFS) and toxicities. Calculating with 20% bilateral Z test (alpha = 0.05, beta = 0.2), 72 patients were needed. From November 2012 to June 2015, seventy-three patients were enrolled and 67 patients were assessable. Fifty-six patients were male and 11 patients were female. The median age was 59 years old. The majority (65.7%) of the patients were diagnosed as squamous cell carcinoma. Severe adverse events were observed in 2 patients (1 hemoptysis and 1 pneumonia). The most common adverse events was leucopenia (95.5%, Grade 3-4:44.8%). The complete response and partial response rate were 11.9% and 64.2%, respectively. The median follow-up time was 37.1 months (20.1-52.1 months). The median time of OS, PFS, and LRFS was 34.7 months, 13.3 months and 27.1 months respectively. The 1-, 2-, and 3-year PFS were 50.7%, 34.8%, and 28.2%, OS were 82.1%, 59.9%, and 47.7%, and LRFS were 72.7%, 54.7%, and 49.9%, respectively. The addition of continuous intravenous human recombinant endostatin to concurrent chemoradiotherapy is effective and tolerable in unresectable stage III NSCLC. Further randomized phase III study is warranted.

P2.02-032 Induction Histology-Based Combination Chemotherapy for Elderly Patients with Inoperable Non-Small Cell Lung Cancer (NSCLC)

SABR is an acceptable treatment of elderly patients with inoperable stage I-II NSCLC; for the stage III, sequential chemoradiotherapy may be appropriate, since it is better tolerated than concurrent chemoradiotherapy. In a prospective phase II not randomized study, patients aged 70 years or more with inoperable stage IIIA and IIIB histologically confirmed squamous cell carcinoma (SCC) or adenocarcinoma NSCLC and ECOG performance status (PS) 0-2, were treated with 3 cycles of induction chemotherapy according to their histology followed by definitive radiotherapy or possible surgery in selected cases. Chemotherapy regimens included: carboplatin at AUC 5 i.v. plus gemcitabine 1000 mg/mq i.v. on days 1,8 or pemetrexed 500 mg/mq i.v. every 21 days in patients with squamous or adenocarcinoma, respectively. Primary endpoint was activity as defined by the overall response rates (ORR) following induction chemotherapy and overall survival (OS); secondary endpoints included feasibility outcome (i.e., toxicity, rate of definitive radiotherapy, chemotherapy dose reduction or withdrawal) and progression-free survival (PFS). Twenty-seven patients, 23 males, 4 females, with a median age of 74 years (range, 70-80), PS=0/1 in 9/15 (33/56%) or 2 in 3 (11%) and median of 2 (range, 0-5) active comorbidities requiring medical treatment were treated. Fourteen patients (52%) had an adenocarcinoma and were treated with carboplatin and pemetrexed, 13 a SCC (42%) with carboplatin and gemcitabine. Eight patients (30%) had a stage IIIA, 19 patients (70%) a stage IIIB. The median cycle of chemotherapy was 3 (range, 1-4). Dose reduction or withdrawal was required in 2 and 3 patients, respectively (18%). ORR was 46% (in 12 of 26 assessable patients); 5 patients with a SCC (42%) and 7 patients with an adenocarcinoma (50%). SD and PD were reported in 4 (15%) and 10 (38%) patients, respectively. Twelve patients (44%) were subsequently treated with radiotherapy, 8 (42%) with stage IIIB and 4 (50%) with stage IIIA. Two patients (7%) with stage IIIA disease underwent lobectomy. With a median follow-up of 10.2 months, 9 patients (33%) were alive and progression-free; median OS and PFS data will be shown. G1-G2 neutropenia, asthenia, anemia, nausea/vomiting and diarrhea were the most frequent toxicity observed in 3 10% of patients and up to 45% for neutropenia. G3-4 neutropenia, asthenia, thrombocytopenia and fever was reported in one patient each (4%), G3 anemia in 2 patients. In a broad elderly NSCLC population induction histology-based chemotherapy seems to be active and feasible in selected patients.

Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer.

PurposeThis study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC).Materials and MethodsFrom May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%).ResultsDuring the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively.ConclusionDefinitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.

Delayed onset of benign pleural effusion following concurrent chemoradiotherapy for inoperable non‐small‐cell lung cancer

Chronic benign pleural effusion (BPE) is a rare complication of concurrent chemoradiotherapy (CRT) for inoperable stage IIIA non-small-cell lung cancer (NSCLC). This report presents three cases of BPE, the workup to differentiate this benign condition from recurrence of cancer and recommends a pleural biopsy as part of the diagnostic process. These inflammatory exudates often remain indolent, and may not require drainage or surgical intervention. In the absence of clinical, radiological and pathological evidence of recurrent disease, we recommend clinicians manage these patients expectantly, using regular clinical assessment and imaging.

Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer.

Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques), treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

Consolidation chemotherapy following concurrent chemoradiation therapy for locally advanced inoperable non-small cell lung cancer

Concurrent chemoradiation therapy is currently a recommended treatment approach for locally advanced inoperable stage ⅢA and stage ⅢB non-small cell lung cancer (NSCLC).There is no consensus on the optimal treatment regimen.It is one of these options for the consolidation chemotherapy following concurrent chemoradiation therapy.To date,there is no sufficient evidence indicating that consolidation chemotherapy following concurrent chemoradiation therapy further improves survival rates.The benefit remains to be confirmed by more clinical test. Key words: Carcinoma, non-small-cell lung; Radiotherapy, adjuvant; Drug therapy, combination; Chemotherapy, adjuvant

A phase I study of nab-paclitaxel (nP) with carboplatin (C) and thoracic radiation (TRT) in patients with locally advanced NSCLC.

7046 Background: One third of patients (pts) with NSCLC present with localized, unresectable disease. Concurrent chemoradiotherapy is well established with weekly paclitaxel and C with median survival of ~14 months. Nanoparticle albumin-bound (nab) paclitaxel (nP) is a cremophor-free formulation of paclitaxel designed to improve solubility and intra-tumor delivery. This phase I trial evaluates weekly nP + C + TRT in pts with unresectable stage III NSCLC. Methods: Pts with inoperable Stage IIIA or IIIB NSCLC, PS 0-1, and FEV 1 >800 ml entered escalating dose cohorts in a modified 3+3 design of nP weekly, beginning at 40 mg/m2 and increasing by 20 mg/m2 increments, in combination with C (AUC 2) weekly for 7 weeks and concurrent RT 66 Gy/33 fractions by either 3D conformal or intensity-modulated techniques. Pts received 2 cycles of consolidation therapy with full dose nP (100 mg/m2 weekly for 3 weeks) and C (AUC 6 on day one of each cycle) every 21d. The DLT period is defined as the concurrent chemoradiation period. Results: Eleven pts were enrolled. Ten pts were treated at 2 dose levels of nP, 40mg/m2 (6 pts) and 60mg/m2 (4 pts). One pt signed consent and then withdrew. Six pts were treated at 40mg/m2 with no DLT. Four pts were treated at 60mg/m2 with 2 DLT of radiation dermatitis and esophagitis. During concurrent treatment, Grade 2 toxicities were fatigue, dehydration, nausea, dysphagia, esophagitis, mucositis, hypoxia, neutropenia, anemia, and thrombocytopenia, and Grade 3 toxicities were neutropenia, mucositis, esophagitis, and dermatitis. No grade 4 toxicities were seen during concurrent treatment. Ten pts were evaluable for response with 9 PR and 1 SD. Seven patients have progressed 3, 5, 6, 7, and 8, 16 and 20 months after enrollment, and 3 patients remain stable at 2, 4, and 28 months. The recommended Phase II dose of weekly nP is 40mg/m2. Conclusions: Weekly nP is safe and well tolerated at 40mg/m2 when used in combination with weekly C (AUC2) and RT (66Gy) with AEs expected for concurrent chemoradiotherapy. A Phase II study to further evaluate this regimen is underway.

High-Dose Conformal Radiotherapy for Patients With Stage III Non–Small-Cell Lung Carcinoma

To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

A phase III trial of carboplatin, paclitaxel, and thoracic radiation therapy with or without thalidomide in patients with stage III non-small cell carcinoma of the lung (NSCLC): E3598

7503 Background: Thalidomide (T) is an oral angiogenesis inhibitor with anti-tumor activity in hematological malignancies. Given that antiangiogenic drugs such as bevacizumab have proven activity in advanced NSCLC, ECOG conducted a phase III study to compare the effects of the addition of thalidomide to paclitaxel/carboplatin/radiation therapy (PC/RT) on overall survival (OS) in pts with newly diagnosed stage III NSCLC. Secondary endpoints included time to progression (PFS) and toxicity. Methods: Pts were required to have inoperable stage IIIA or IIIB (no pleural effusion) NSCLC and a PS of 0 or 1. Pts were randomized to receive 2 cycles of P (225 mg/m2)+ C (AUC=6) every 3 wks or PC + thalidomide starting at 200 mg daily with the possibility of dose escalation. This was followed by weekly C (AUC=2), P (45 mg/m2) and concurrent RT (60 Gy) ± T. Pts on PC/RT + T continued thalidomide for 24 mo. or until disease progression. Results: 277 eligible pts were randomized to PC/RT and 272 pts to PC/RT + T. Median age was 63; 61% of pts had stage IIIB disease, 35% had squamous histology, and 46% were PS 0. The third planned interim analysis was conducted with 403 of 506 planned deaths (73.9%) for full analysis and the trial was stopped early by the ECOG Data Monitoring Committee for futility. The median overall survival for the no T arm was 15.3 mo. (12.4–20.2 mo.) compared to 16.0 mo for the T arm (14.4–18.3 mo.); hazard ratio = 0.985 (0.81–1.19); p = 0.88. Median PFS for the no T arm was 7.6 mo. (6.6–8.7 mo.) compared to 8.0 mo. for the T arm (7.1–9.1 mo.), p&gt;0.05. The most common toxicity on both arms was myelosuppression. 11% of pts on the T arm had a grade 3–5 thrombosis/embolism, compared to &lt;3% on the no T arm. Conclusions: The addition of thalidomide to PC/RT in pts with stage III NSCLC does not provide a clinically significant benefit. [Table: see text]

Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB Non–Small-Cell Lung Cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group

Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB Non–Small-Cell Lung Cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group

Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB Non–Small-Cell Lung Cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group

The aim of this study was to examine whether, after preceding induction chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone. Patients with non-small-cell lung cancer in inoperable stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel 200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without progression at restaging after induction chemotherapy were randomly assigned to radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The primary end point was overall survival; secondary end points were time to progression, response, and toxicity. Three hundred three patients entered the study, and 276 completed induction chemotherapy. Two hundred fourteen patients were randomly assigned (radiotherapy alone: n = 113; simultaneous chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and median follow-up time of the subgroup of censored patients (n = 52) was 37.4 months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the induction phase were mild. During radiotherapy, overall toxicity rates were not significantly different between the two arms. Median survival times in the radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to 16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not statistically significant, P = .091). Median time to progression significantly favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months) versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log-rank test). Induction chemotherapy followed by chemoradiotherapy with weekly paclitaxel is feasible. Response, time to progression, and survival favor chemoradiotherapy compared with radiotherapy alone.

Cisplatin(P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial

7103 Background: We previously reported that triplets with P-gemcitabine (G) plus vinorelbine (V) (PGV) or paclitaxel (T) (PGT) prolonged the survival (S) of advanced NSCLC patients (pts) in comparison with P-based doublets (PG or PV). Aims of the present study were: (1) to compare (log-rank test) the S of P-based triplets vs P-free doublets, and (2) to compare (Fisher test) safety and response rate (RR) of T- and V-regimens. Methods: A 2x2 factorial design was adopted. Pts aged ≤ 70 years, with PS (ECOG) &lt; 2, inoperable stage IIIA, IIIB, or IV NSCLC were randomly treated with: GV = G 1,000 mg/m2 + V 25 mg/m2 on day (D) 1 and 8; GT = G 1,000 mg/m2 + T 125 mg/m2 on D 1 and 8; PGV = P 50 mg/m2 on D 1 and 8 + GV; PGT = P 50 mg/m2 on D 1 and 8 + GT. In all arms, cycles were repeated Q 3 weeks. Only responder pts after 3 cycles received further chemotherapy (CT). Thoracic RT was delivered after CT to pts with intra-thoracic disease. 330 events were required to have a 90% power to demonstrate (two-sided P &lt; 0.05) a 30% reduction of hazard of death. Results: From April 2001 to December 2005, 431 pts were recruited in the 4 arms. Characteristics in % were well balanced in P-based triplets and P-free doublets: males, 84/91; PS 0, 25/23; squamous cell carcinoma, 38/42; weight loss, 22/29; stage IV, 66/65; CNS metastases, 5/8; ≥ 2 metastatic sites, 29/30. So far, 411 pts were assessed for response: RR of triplets vs doublets was 88/204 (43%) vs 68/207 (33%) (P = 0.020), and of T-based vs V-based regimens was 40% vs 36% (P = 0.218). To date, 313 deaths were registered: median and 1-year S were 10.6 mo. and 41% for pts treated with triplets, and 10.4 mo. and 39% for pts treated with doublets (P = 0.786). Over initial 3 courses, occurrence of grade ≥ 3 toxicity (T vs V, % pts) was: neutropenia, 18% vs 30% (P &lt; 0.004); febrile neutropenia, 4% vs 7%; platelets, 7% vs 12% (P = 0.056); anemia, 5% vs 7%; vomiting, 1% vs 2%; diarrhea, 6% vs 3%; stomatitis, 3% vs 0.5%. Grade ≥ 2 neurotoxicity occurred in 1% of both groups. Conclusions: Activity was significantly higher with P-based triplets, but they did not affect the OS. T-based regimens were equally active and less toxic than V-based regimens. Therefore, the GT regimen may represent a new standard of care for advanced NSCLC pts. No significant financial relationships to disclose.

52 A pilot study of celecoxib with docetaxel/radiation and consolidation docetaxel/cisplatin in inoperable stage IIIa and IIIb non-small cell lung cancer (NSCLC)

52 A pilot study of celecoxib with docetaxel/radiation and consolidation docetaxel/cisplatin in inoperable stage IIIa and IIIb non-small cell lung cancer (NSCLC)

Concurrent paclitaxel, carboplatin and radiation therapy for locally advanced non-small cell lung cancer

7336 Background:Standard therapy for inoperable stage III NSCLC is chemoradiotherapy. But optimal combination of these two modality is not established. To evaluate the efficacy and safety of chemoradiotherapy with a concurrent use of paclitaxel and carboplatin plus thoracic radiation for locally advanced NSCLC. Methods:The study is a phase II multi-institutional trial. Eligible patients had inoperable stage IIIA or IIIB disease, except cases with pleural or pericardial effusion, ECOG performance status 0 or 1, and no previous treatment. Paclitaxel (45 mg/m2) and carboplatin (AUC = 2) were administered every 7 days for 10 weeks. When PR was observed, chemotherapy was extended upto 16 weeks. Radiation therapy were concurrently administered 1.8∼2.0 Gy/day for 5∼7 week (total 60∼65 Gy). Results:Registration has finished on December 2002. Among the 72 patients registared, 68 patients were eligible and toxicity was evaluated for the 68 patients. There were 16 patients with stage IIIA and 52 with stage IIIB disease. The median age was 63.5 years (38–74). There were 33 patients with adenocarcinoma, 31 with squamous cell carcinoma and 3 with large cell carcinoma, one with undifferentiated carcinoma. The hematologic toxicities >= grade 3 were 24% leukopenia, 6% neutropenia, 3% thrombocytopenia, 12% anemia. There were 3 cases with treatment related death. One patient died of pulmonary toxicity, one with hemorrhage due to radiation necrosis, and one with pneumocystis carinii pneumonia which occurred after the recovery from hematologic toxicity. The response rate (intent-to-treat base) was 65% with 4 CR, 40 PR. Median follow-up time was 28 months and median survival has not been reached, and 1 year- and 2 year-survival (estimated survivals) were 57% and 41%, respectively. Conclusions:Concurrent use of radiation and paclitaxel plus carboplatin is active and promising regimen to stage III NSCLC. Updated survival data is to be presented. No significant financial relationships to disclose.

Concurrent paclitaxel, carboplatin and radiation therapy for locally advanced non-small cell lung cancer

7336 Background:Standard therapy for inoperable stage III NSCLC is chemoradiotherapy. But optimal combination of these two modality is not established. To evaluate the efficacy and safety of chemoradiotherapy with a concurrent use of paclitaxel and carboplatin plus thoracic radiation for locally advanced NSCLC. Methods:The study is a phase II multi-institutional trial. Eligible patients had inoperable stage IIIA or IIIB disease, except cases with pleural or pericardial effusion, ECOG performance status 0 or 1, and no previous treatment. Paclitaxel (45 mg/m2) and carboplatin (AUC = 2) were administered every 7 days for 10 weeks. When PR was observed, chemotherapy was extended upto 16 weeks. Radiation therapy were concurrently administered 1.8∼2.0 Gy/day for 5∼7 week (total 60∼65 Gy). Results:Registration has finished on December 2002. Among the 72 patients registared, 68 patients were eligible and toxicity was evaluated for the 68 patients. There were 16 patients with stage IIIA and 52 with stage IIIB disease. The median age was 63.5 years (38–74). There were 33 patients with adenocarcinoma, 31 with squamous cell carcinoma and 3 with large cell carcinoma, one with undifferentiated carcinoma. The hematologic toxicities >= grade 3 were 24% leukopenia, 6% neutropenia, 3% thrombocytopenia, 12% anemia. There were 3 cases with treatment related death. One patient died of pulmonary toxicity, one with hemorrhage due to radiation necrosis, and one with pneumocystis carinii pneumonia which occurred after the recovery from hematologic toxicity. The response rate (intent-to-treat base) was 65% with 4 CR, 40 PR. Median follow-up time was 28 months and median survival has not been reached, and 1 year- and 2 year-survival (estimated survivals) were 57% and 41%, respectively. Conclusions:Concurrent use of radiation and paclitaxel plus carboplatin is active and promising regimen to stage III NSCLC. Updated survival data is to be presented. No significant financial relationships to disclose.

Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): A multicenter randomized trial

Purpose: The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity, reasonable activity and easy out-patient administration. Purpose of our present prospective study was to evaluate the dose-response relationship of paclitaxel.Patients and methods: Since July 1996, 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial. Ninety nine patients (group A) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 (group B) to receive the same regimen with paclitaxel increased to 225 mg/m2 Eligibility criteria included WHO performance status 0–2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis, no prior chemotherapy and adequate renal and hepatic function. Patients in both groups were well-matched with baseline disease characteristics.Results: In group A with 90 evaluable patients, the response rate was 25.6%(6 CR, 17 PR) whereas in group B with 88 evaluable patients, the response rate was 31.8% (3 CR, 25 PR), P = 0.733. Median time to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months, P = 0.044). The median survival was 9.5 months for group A versus 11.4 months for group B (P = 0.16). The one-year survival was 37% for group A and 44% for group B (P = 0.35). The best prognostic factor for one-year survival was the response rate (P < 0.0001). With a relative dose intensity of paclitaxel 0.94 in both groups, neurotoxicity (P =0.025) and leucopenia (P = 0.038) were more pronounced in group B patients. No toxic death was observed.Conclusions: Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia. The better response rate, the longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant.