Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.     

Gemcitabine and cisplatin as induction chemotherapy for patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma: an Italian Lung Cancer Project Observational Study

BACKGROUND: The objective of this trial was to evaluate the activity and safety of one of the newer platinum-based doublets as a neoadjuvant regimen in patients with unresectable Stage IIIA-bulky N2 and Stage IIIB nonsmall cell lung carcinoma (NSCLC). METHODS: From June 1996 to April 2000, 129 consecutive patients with locally advanced NSCLC were treated with gemcitabine, 1000 mg/m(2) on Days 1 and 8 and cisplatin, 70 mg/m(2) on Day 2 (GC) of a 21-day treatment cycle, for 4 cycles, as part of a combined-modality approach. RESULTS: After induction chemotherapy, 80 patients (62%; 95% confidence interval, 53.6-70.4%) achieved a partial response, 43 patients (33%) had stable disease, and 6 patients (5%) had disease progression during chemotherapy. Forty patients (31%), were considered resectable and underwent thoracotomy. Complete resectability was obtained in 38 patients (29%), with 2% of patients achieving a pathologic complete response. After surgery, 9 patients with Mountain Classification Stage IIIA NSCLC and 9 patients with Stage IIIB NSCLC received definitive adjuvant radiotherapy. Forty-six of 52 patients with Stage IIIB disease and 24 of 37 patients with Stage IIIA disease who were not considered suitable for surgery received definitive radiotherapy. The median time to disease progression was 11.4 months, the median survival was 19.4 months (range, 1.2-55.2 + months), and the 1-year survival rate was 74%. The lungs (33%) and the brain (21%) were the main sites of recurrence. Major toxicity was comprised of Grade 3-4 thrombocytopenia, which occurred in 34 patients (27%). CONCLUSIONS: GC administered according to a 3-week schedule was a highly active and safe regimen in patients with primary, unresectable, locally advanced NSCLC.     

Aggressive Treatment of Primary Tumor in Patients With Non–Small-Cell Lung Cancer and Exclusively Brain Metastases

Between 30% and 50% of patients with non–small-cell lung cancer (NSCLC) will develop cerebral metastases in the course of their illness. As improvements are made in the local brain treatment, the question arises on how to manage patients with NSCLC who have solely stable brain metastatic disease and if treatment should be considered for the primary lung lesion. The present article will review published series of patients with NSCLC and with brain metastases treated with aggressive thoracic management, with either lung tumor resection or thoracic radiation with or without chemotherapy as definitive treatment. We will also assess which prognostic factors may be useful in the identification of the subset of patients who could benefit from this more aggressive approach. For patients treated with surgical resection for the primary lung tumor, median survival ranged from 19 to 27 months, and the 1-, 2-, and 5-year survival reached 56%-69%, 28%-54%, and 11%-24%, respectively. Patients treated with aggressive radiotherapy with or without chemotherapy, achieved a median survival of 15.5-31.8 months, with a 1-year survival of 50%-71%, and a 2-year survival of 16%-60%. Well-selected patients with NSCLC and with exclusively oligometastatic cerebral disease represent a subgroup of patients with stage IV NSCLC that might achieve long-term survival after treatment directed to the brain and lung tumor lesions. Patients with N0 or N1 disease may be selected for surgical thoracic treatment, whereas those with N2 or N3 disease may benefit from combined chemoradiotherapy in the absence of progression after induction chemotherapy.     

Phase II study of induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with oral etoposide and cisplatin in patients with inoperable stage III non-small-cell lung cancer

PURPOSE: For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin. METHODS AND MATERIALS: Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss < or =5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m2 and vinorelbine 30 mg/m2, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m2 on Days 1 and 8) were given concurrently 4 weeks apart. RESULTS: Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients. CONCLUSIONS: Induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with etoposide and cisplatin showed very promising survival in patients with Stage III NSCLC, especially in those without supraclavicular nodal involvement, which warrants further evaluation.     

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain

BACKGROUND: The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall-cell lung cancer (NSCLC). METHODS: Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI). RESULTS: Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty-two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5-year estimates of brain metastasis-free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively. CONCLUSION: Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed.     

Induction chemotherapy employing dose-intense cisplatin with mitomycin and vinblastine (MVP400), followed by thoracic surgery or irradiation, for patients with stage III nonsmall cell lung carcinoma.

BACKGROUND: Cisplatin-based induction chemotherapy before surgery or irradiation has improved the survival of patients with Stage III nonsmall cell lung carcinoma (NSCLC). Encouraged by earlier results with preoperative MVP (cisplatin [120 mg/m(2) or 25 mg/m(2)/week], vinblastine, and mitomycin) for Stage IIIA patients with clinically apparent mediastinal (N2) disease, the authors conducted a Phase II trial of the safety and efficacy of induction MVP400 with the dose intensity of cisplatin doubled from 25 to 50 mg/m(2) per week. METHODS: From October 1992 to March 1996, 37 patients with Stage IIIA (26) or Stage IIIB (11) NSCLC began the MVP400 induction chemotherapy program. Four doses of cisplatin (100 mg/m(2)), 7 doses of vinblastine, and 2 doses of mitomycin were given over 9 weeks. Patients received either surgery or irradiation after induction treatment. RESULTS: Overall, the response rate was 65% (95% confidence interval, 49-81%) with a complete resection rate of 67%. The median survival was 17 months, with 66% of patients alive at 1 year. Complete resection and Stage IIIA involvement were favorable prognostic indicators for survival. No Stage IIIB patients underwent a complete resection. Myelosuppression was the most common side effect. There were no treatment-related deaths. CONCLUSIONS: Although high response and complete resection rates were again demonstrated, results with the MVP400 regimen were not improved over those achieved with MVP regimen tested earlier with Stage IIIA (N2) patients. The authors continue to recommend MVP as an induction chemotherapy regimen for clinical trials.     

Gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: a phase II study

BACKGROUND: The authors conducted a Phase II study to evaluate the activity of the combination of gemcitabine and vinorelbine in patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Patients were eligible if they had Stage IIIB (malignant pleural effusion) or Stage IV NSCLC, no prior chemotherapy, and Cancer and Leukemia Group B performance status (PS) 0-2. Patients with brain metastases were eligible if they were neurologically stable after brain irradiation. Thirty-three patients from participating institutions were enrolled. One patient was ineligible due to untreated brain metastases. Patients were treated with gemcitabine 1250 mg/m(2) over 30 minutes (1000 mg/m(2) for the first 6 patients) and vinorelbine 25 mg/m(2) over 6 minutes, both administered intravenously on Days 1 and 8 every 21 days. Treatment was planned for a total of six cycles or more if the patient had persistent benefit. Growth factors were not allowed. RESULTS: Among all 32 eligible patients, there were 8 partial responses, for an overall response rate of 25% (95% confidence interval [CI], 11.5-43. 4%). The median survival time was 8.3 months and the 1-year survival rate was 38% (95% CI, 24-59%). Patients with PS 0-1 had a median survival of 11.7 months and a 1-year survival rate of 48%. Grade 3 and 4 neutropenia was observed in 13% and 25% of the 148 treatment cycles, respectively. One patient died of neutropenic sepsis. Only 2 episodes of Grade 3 and 4 thrombocytopenia were observed. Nonhematologic toxicity was minimal. CONCLUSIONS: Gemcitabine and vinorelbine is an active and well-tolerated regimen in patients with advanced NSCLC, with response and survival rates at least comparable to those achieved with standard platinum-based regimens. This combination may be particularly suitable for the elderly or for patients who cannot tolerate more toxic platinum-based regimens.     

Treatment outcome for patients with primary nonsmall-cell lung cancer and synchronous brain metastasis

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS.     

Role of multimodality treatment for lung cancer

Locally advanced non-small cell lung cancer (NSCLC) is, in fact, a systemic disease requiring a multimodality approach for optimal treatment. The role of preoperative chemotherapy has been established and is now an accepted treatment for resectable Stage IIIA NSCLC. Several studies have addressed the feasibility and efficacy of preoperative chemotherapy followed by surgery. All these induction chemotherapy trials have reported a high radiographic response rate, high respectability rate and improved survival in completely resected patients. The findings of three published randomized trials indicate that the survival rate of Stage IIIA patients is better with induction chemotherapy plus surgical resection than with resection alone. More recently, Phase II trials using concurrent chemoradiotherapy have been tested with encouraging results. Chemo-therapy combined with thoracic radiotherapy has emerged as a primary treatment option for locally advanced, unresectable NSCLC. Randomized trials and subsequent meta-analyses have shown a clear survival benefit with platinum-based combination chemotherapy administered with thoracic radiation-as compared to radiation alone-in treating inoperable Stage IIIA and IIIB lung cancer. Combined modality treatment in locally advanced NSCLC continues to evolve and is the subject of ongoing research. Despite clinical advances, many aspects of the management of these patients are yet to be fully clarified: Is surgical resection really necessary for Stage IIIA patients? What is the value of altered-fractionation radiotherapy and three-dimensional conformal radiation therapy? What is the optimal sequencing of radiotherapy and chemotherapy? In this regard, new chemotherapeutic agents may provide additional benefits in the multimodality approach, and it is for this reason that various studies are underway which have incorporated new agents in the front line setting. Finally, a better understanding of the biology of tumors could well help us to optimize treatments. In the future, molecular classification of NSCLC may provide a useful tool when making therapy-related decisions.     

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer

Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer (NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient’s life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence (distant, locoregional or combined) and the treatment modality: (1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage IV disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC; (2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice for oligometastatic recurrence; and (3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage IIIA and IIIB disease.     

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.     

Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven Stage IIIA(N2) nonsmall cell lung carcinoma: a Phase II multicenter study

BACKGROUND: The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). METHODS: Forty-nine chemotherapy-na?ve patients (median age, 61 years; World Health Organization performance status, 0-1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m(2) gemcitabine, 125 mg/m(2) paclitaxel, and 50 mg/m(2) cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3-4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. CONCLUSIONS: GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored.     

Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung.

BACKGROUND: The incidence of bronchioloalveolar carcinoma of the lung (BAC), a pathologically distinct type of nonsmall cell lung carcinoma (NSCLC), appears to be rising. In this study, the authors compared data on the clinical presentation and clinical courses of patients with Stage IIIB and IV BAC with data on other types of NSCLC. METHODS: The authors collected clinical, radiographic, and pathology information about 28 patients with Stage IIIB and IV BAC and 124 patients with other histologic types of NSCLC. RESULTS: Twelve of 28 BAC patients (43%) were women, compared with 40 of 124 control patients (32%). Nine (32%) of the patients with BAC had never smoked cigarettes, versus 20 controls (16%) (P = 0.02). Eighteen patients (64%) with BAC had bilateral multilobar or multicentric pulmonary involvement, compared with 13 controls (15%) (P < 0.001). Patients with advanced stage (IIIB and IV) BAC had a median survival of 15 months from the time of diagnosis; for patients with other types of Stage IIIB and IV NSCLC, had a median survival of 10 months (P = 0.01). CONCLUSIONS: Patients with BAC of the lung have clinical, radiographic, and pathologic characteristics that distinguish them from patients with other types of NSCLC. A greater proportion of women and nonsmokers present with BAC than with other types of NSCLC. Patients with advanced stage BAC are more likely to have bilateral diffuse pulmonary involvement, are less likely to develop brain metastases, and have longer survival than patients with other types of Stage IIIB and IV NSCLC. Further research is warranted to define etiology, molecular abnormalities, and more effective therapeutic interventions.     

Survival analysis after resection of metastatic disease followed by peptide vaccines in patients with Stage IV melanoma

BACKGROUND: Metastatic melanoma carries a poor prognosis, with a median survival of 7-9 months. Surgical resection of metastatic disease has been advocated to improve survival. Immunotherapy after metastasectomy may further improve the outcome for high-risk resected disease. METHODS: Charts from patients treated on institutional vaccine trials were analyzed. Patients with American Joint Committee on Cancer (AJCC) Stage IV melanoma who underwent surgical resection of metastatic sites followed by treatment on a peptide vaccine trial were eligible for this study. Survival was calculated from the date of enrollment on the clinical trial. RESULTS: Forty-one patients met inclusion criteria. The median age was 56.5 years, with approximately equal numbers of men and women. The ECOG performance status was 0 in all patients. Approximately 46% of patients underwent resection of visceral metastases before vaccine. The median follow-up was 5.6 years. The median overall survival was 3.8 years. CONCLUSIONS: In selected patients with AJCC Stage IV melanoma, resection of metastatic disease followed by vaccine therapy can result in long-term survival.     

Nuclear survivin predicts recurrence and poor survival in patients with resected nonsmall cell lung carcinoma

BACKGROUND: Survivin, which is a member of the inhibitor of apoptosis protein gene family, regulates both programmed cell death and mitosis. It has been shown that survivin expression and its subcellular localization both have prognostic value for patients with malignant disease. In this study, the authors investigated whether nuclear or cytoplasmic staining of survivin was a prognostic marker for patients with lung carcinoma. METHODS: Paraffin-embedded tissue blocks from 144 patients with Stage I and II resected nonsmall cell lung carcinoma (NSCLC) were obtained for immunohistochemical staining. Three specimens from each patient were prepared and stained with a survivin-specific antibody. Nuclear and cytoplasmic staining was graded from 1 to 3 based on intensity. RESULTS: Patients who had nuclear staining for survivin had a significantly increased risk of disease recurrence (hazard ratio, 2.95; P = 0.0046) and death (hazard ratio, 2.74; P = 0.0086). CONCLUSIONS: The nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with resected Stage I and II NSCLC.     

Phase II trial of weekly paclitaxel and gemcitabine for previously untreated, stage IIIB-IV nonsmall cell lung cancer

BACKGROUND: The purpose of the current study was to evaluate the efficacy and tolerance of the noncisplatin-based combination of paclitaxel and gemcitabine administered weekly for patients with untreated metastatic nonsmall cell lung cancer (NSCLC). METHODS: Patients with Stage IIIB/IV or recurrent NSCLC, a performance status of 0-2, and no prior chemotherapy exposure were eligible. Patients received gemcitabine 1000 mg/m2 and paclitaxel 85 mg/m2 on Days 1, 8, 15, 22, 29, 36 of an 8-week cycle until progression. RESULTS: Thirty-nine eligible patients were enrolled. The median age was 66 years and 14 patients were > or =70 years old. Performance status was 2 in 13 (33%) and 29 patients (75%) had Stage IV. Five patients (12.8%) developed interstitial pneumonitis and 2 of these were responsive to steroid therapy. The overall response rate was 23.1%, with no complete responses. The median survival was 32 weeks and the 1-year survival was 32%. CONCLUSIONS: This regimen of weekly paclitaxel and gemcitabine has modest activity in advanced NSCLC.     

Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma. Brain metastases have been reported to be a common feature of Stage IV ASPS, and recent practice guidelines recommend routine intracranial imaging as part of the staging evaluation in all patients who present with ASPS. METHODS: The authors performed a comprehensive retrospective review of the clinical presentation, treatment, outcome, and patterns of failure in a consecutive series of patients with localized (American Joint Committee on Cancer [AJCC] Stages II/III) or metastatic (AJCC Stage IV) ASPS who presented to a tertiary care cancer center between 1959 and 1998. RESULTS: Seventy-four patients were identified from the database searches. The anatomic distribution of their primary tumors included: extremities, 44 patients (60%); trunk, 15 patients (20%); head and neck, 9 patients (12%); and retroperitoneum, 6 patients (8%). The median tumor size was 6.5 cm (range, 1.2-24 cm). The AJCC stage at presentation was Stage II or III in 35% of the patients and Stage IV in 65% of the patients. The 5-year actuarial local recurrence free, distant recurrence free, disease free, and overall survival rates among the 22 patients with localized ASPS were 88%, 84%, 71%%, and 87%, respectively. At a median follow-up of 9 years, 2 of 22 patients with localized disease had developed local recurrences and 3 had developed metastatic disease (all to the lung only). Brain metastases were noted in 9 of 48 patients who presented with Stage IV (M1) disease (19%) and always were noted in association with metastasis to other sites. The median survival of patients with M1 disease was 40 months, with a 5-year survival rate of 20%. CONCLUSIONS: Long term follow-up of patients with localized ASPS reveals a relatively indolent clinical course with relatively low rates of local and distant recurrence. In patients with Stage IV ASPS, brain metastases were observed only as part of more disseminated disease. The observations of the current study do not support current practice guidelines for the staging of patients with ASPS and suggest that selective rather than routine intracranial imaging should be used in patients presenting with ASPS.     

吉非替尼治疗50例非小细胞肺癌脑转移的临床分析

背景与目的：非小细胞肺癌（non-small cell lung cancer,NSCLC）脑转移较常见,预后不佳。吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂,多应用于治疗晚期NSCLC。本研究拟探讨吉非替尼治疗NSCLC脑转移的疗效、预后及其相关因素。方法：回顾性分析50例NSCLC脑转移患者的临床资料,所有患者均口服吉非替尼250mg/d,直到疾病进展、死亡或发生不可耐受的不良反应。疗效分析采用χ2检验,生存分析采用Kaplan-Meier法并进行Log-rank时序检验,用Cox比例风险模型进行多因素分析。结果：吉非替尼对颅内病灶的疗效为部分缓解5例（10%）,疾病稳定37例（74%）,疾病进展8例（16%）,客观有效率为10%,疾病控制率为84%。全身病变的总体疗效为部分缓解5例（10%）,疾病稳定30例（60%）,疾病进展15例（30%）,客观有效率为10%,疾病控制率为70%。总体疾病控制率与患者的PS评分、脑转移数目具有相关性（P分别为0.004和0.022）,但与年龄、性别、吸烟状况、病理类型、脑转移时间、化疗及放疗与否和不良反应等临床特点未见有相关性（P均〉0.05）。中位疾病进展时间为7.0个月,与患者的PS评分及吸烟状况具有相关性（P分别为0.000和0.045）。中位生存期为10.8个月,1、2年生存率分别为44%和6%。单因素分析显示生存期与患者的PS评分、吸烟状况和脑转移数目具有相关性（P分别为0.011、0.028和0.044）,多因素分析则显示生存期与患者的PS评分、吸烟状况具有相关性（P分别为0.005和0.006）,与脑转移数目接近有统计学意义（P=0.075）。结论：吉非替尼对NSCLC脑转移具有一定的疗效,功能状态良好（PS0～1分）的非吸烟患者具有较好的生存获益,单发脑转移的生存时间有好于多发脑转移的趋势。吉非替尼可以作为NSCLC脑转移的一种治疗选择。     

Neoadjuvant chemoradiotherapy of stage III non-small-cell lung cancer

Twenty to 30% of patients with non-small-cell lung cancer (NSCLC) in stage III are not resectable primarily with 5-year survival less than 10%. Since the majority of patients die from metastases, efforts have been made in the past to improve prognosis by application of neoadjuvant chemoradiotherapy regimens followed by subsequent resection. In a phase II study performed between 1993 and 1998, 93 patients in stage III (IIIA, 16%; IIIB, 84%) received an induction chemotherapy consisting of two cycles cisplatin (100 mg/m²) and vindesine (3 mg/m²) with subsequent sequential radiotherapy of 36 Gy. Sixty-five patients demonstrated partial or complete remission. Sixty underwent surgery; in 49 of them complete resection was possible. Five-year survival in the whole group was 24%, and that in the surgical cohort 39%. Six patients had no residual tumor. Postoperative N0 status was associated with a 5-year survival of 75%, and stage N1–3 with 13%. Thirty-day mortality was 7% postoperatively. Neoadjuvant chemoradiotherapy can significantly improve long-term survival in stage III NSCLC with an acceptable therapy-induced mortality.     

Phase II study of weekly irinotecan plus capecitabine for chemotherapy-naive patients with advanced nonsmall cell lung carcinoma

BACKGROUND: A Phase II study was conducted to evaluate the efficacy and toxicity of an irinotecan plus capecitabine combination, a new nonplatinum regimen, in chemonaive patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Between July 2003 and April 2004, 53 patients with a histologically confirmed diagnosis of NSCLC were enrolled. All but 5 patients were male, 52 (98%) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, 39 (74%) had AJCC Stage IV disease, and the median age was 61 years. Treatment consisted of intravenous irinotecan at a dose of 90 mg/m(2) on Days 1 and 8 and oral capecitabine at a dose of 1000 mg/m(2) twice daily on Days 1-14 of each 21-day cycle, given up to 12 cycles. RESULTS: Of 53 patients enrolled, 22 achieved objective tumor responses (all partial responses) for an overall response rate of 41.5% (95% confidence interval [95% CI], 28.2-54.8%). After a median follow-up of 17.4 months, the median survival was 14.6 months with a 1-year survival rate of 60.1% (95% CI, 46.9-73.4%) and a median progression-free survival of 5.1 months. Treatment was very well tolerated, with only 10% of patients experiencing NCI-CTC Grade 3 or 4 toxicities. The most common toxicities were hand-foot syndrome and diarrhea. In multiple logistic regression analysis for overall response, only the stage predicted for significantly better response (P = 0.04). Squamous cell carcinoma was marginally predictive for better response (P = 0.08). CONCLUSIONS: The irinotecan plus capecitabine regimen demonstrated an antitumor activity that is favorably comparable with other commonly used cisplatin-based regimens. Given the mild toxicity profile and favorable survival outcome, this nonplatinum regimen warrants further evaluation in a randomized trial.