[Case of double primary cancer (lung cancer and minute cancer of the stomach in the early stage)].
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Humans↗
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Creatinine kinase-BB isoenzyme as a tumor marker in breast cancer, lung cancer, and lymphoma.
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Adult↗
Interstitial lung disease, lung cancer, lung transplantation, pulmonary vascular disorders, and sleep-disordered breathing in AJRCCM in 2004.
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Female↗
Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.
Adult↗
Immunohistochemical and histochemical markers of primary lung cancer, lung metastases, and pleural mesotheliomas.
Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.
Adenocarcinoma↗
EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups.
BACKGROUND: Preclinical evidence suggests that retinoids and antioxidants may prevent or delay the occurrence of cancer in the upper or lower airways, but such effects have not been reliably established in clinical studies. To assess the chemopreventive effects of vitamin A (retinyl palmitate) and N-acetylcysteine, we conducted a large randomized intervention study in patients with head and neck cancer or with lung cancer, most of whom had a history of smoking. METHODS: From June 1988 through July 1994, a total of 2592 patients (60% with head and neck cancer and 40% with lung cancer) were randomly assigned to receive 1) retinyl palmitate (300000 IU daily for 1 year followed by 150000 IU for a 2(nd) year), 2) N-acetylcysteine (600 mg daily for 2 years), 3) both compounds, or 4) no intervention. All statistical tests were two-sided. RESULTS: Of the patients, 93.5% had smoked tobacco at sometime in their lives (and 25% continued to smoke after cancer diagnosis). After a median follow-up of 49 months, 916 patients were reported with an event (recurrence, second primary tumor, or death). No statistically significant difference was observed in overall survival or event-free survival between patients who received retinyl palmitate and patients who did not. Similarly, no difference was seen in overall survival or event-free survival between patients who received N-acetylcysteine and patients who did not. There was a lower incidence of second primary tumors in the no intervention arm, but the difference was not statistically significant. CONCLUSION: A 2-year supplementation of retinyl palmitate and/or N-acetylcysteine resulted in no benefit-in terms of survival, event-free survival, or second primary tumors-for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.
Acetylcysteine↗
Malignant disease appearing late after operation for T1 N0 non-small-cell lung cancer. The Lung Cancer Study Group.
Occurrences of malignancy in 308 patients who were clinically free of cancer 60 months or more after surgical treatment of T1 N0 non-small-cell lung cancer are summarized. At last report, 210 patients remained alive with no evidence of malignant disease, 43 patients died of nonmalignant causes, and 55 patients had 59 occurrences of malignant disease. Late lung cancer recurrence was observed in 22 patients (concurrent with nasopharyngeal cancer in one patient and with laryngeal cancer in one patient). Metachronous second lung cancer was noted in 20 patients (including concurrent colon cancer in one patient and metastatic recurrence in one patient). Other nonpulmonary malignant tumors appeared in 13 patients. Including second lung cancer, 25 cancers of aerodigestive epithelium were observed in 23 patients. The malignancy-free survival advantage for patients with squamous cancer observed until 60 months after resection was not sustained at 60 months and beyond. At the time of last follow-up, 84 patients (27%) had died; 43 were free of malignancy, and 41 had malignancy (14 patients were alive with malignancy and 210 with no evidence of disease). These data reinforce two conclusions: (1) The probability of lung cancer recurrence or appearance of new lung cancer 5 years or more after successful operation in this select subpopulation of patients with lung cancer is of concern. (2) The malignancy-free survival advantage of patients with squamous cancer disappears after 5 years.
Adult↗
A preliminary evaluation of calcitonin and PDN-21 as tumor markers for lung cancer. EORTC Lung Cancer Working Party.
Immunoreactive calcitonin (iCT) can be ectopically secreted by lung cancer cells and has been proposed as a tumor marker for bronchial neoplasms. Since PDN-21 (katacalcin or the carboxyl-terminal flanking peptide of the calcitonin gene) and CT are cosecreted in normal subjects and in patients with medullary thyroid carcinoma (MTC), we sought to determine the potential utility of PDN-21 as a tumor marker for lung cancer. We measured carcinoembryonic antigen (CEA), neurone-specific enolase (NSE), iCT, and PDN-21 in 119 to 378 healthy subjects, 88 to 91 patients with benign pulmonary disease, and 249 patients with advanced lung cancer (108 small cell lung cancers and 141 other forms). Tumor marker specificity was satisfactory: the percentage of increased values (greater than the 95th percentile of normal subjects) in patients with benign pulmonary diseases varied from 9% (NSE, PDN-21) to 12% (CEA). PDN-21 was a more sensitive marker for lung cancer than iCT: the percentage of increased values was 44% for PDN-21 versus 19% for iCT, and 51% versus 23% for the subgroup of patients with small cell lung cancer (SCLC). PDN-21 concentrations were increased in 69 (34%) of 202 patients with a normal iCT level, whereas iCT concentrations were increased in only six (4%) of 139 patients with a normal PDN-21 level. However, markedly elevated concentrations of the two markers generally occurred in the same patients and the correlation between the two markers was significant (rs = 0.60; P less than 0.01). PDN-21 provided complementary information to that from the classical markers NSE and CEA.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small-cell lung cancer. The Lung Cancer Study Group.
BACKGROUND: Most studies of adjuvant chemotherapy, radiotherapy, or immunotherapy in non-small-cell lung cancer patients with complete surgical resection of disease have shown negative results. However, two studies of stage II and III disease by our Lung Cancer Study Group suggested an advantage to adjuvant therapy with cyclophosphamide, doxorubicin, and cisplatin (CAP). PURPOSE: Since neither of those studies had an untreated control, the Lung Cancer Study Group undertook a trial that included a control group and also offered the potential benefit of adjuvant therapy with CAP to patients with T1, N1 or T2, N0 (stage I) non-small-cell lung cancer. METHODS: After complete resection, eligible patients with stage I disease were classified by known prognostic factors and randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery. The CAP regimen consisted of 400 mg/m2 cyclophosphamide, 40 mg/m2 doxorubicin, and 60 mg/m2 cisplatin. Stratification by prognostic factors was as follows: histology (squamous versus nonsquamous), white blood cell count before surgery (> or = 9100/mm3 versus < 9100/mm3), and Karnofsky performance status before surgery (< or = 90% versus 100%). RESULTS: Of the 269 patients entered in the study, 101 had recurrence and 127 have died. Mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival (not stratified by histology) between the two groups, even when analyses were adjusted for prognostic variables. There was one treatment-related death on the CAP arm due to infection during neutropenia. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles on time. In 74% of the patients, the site of initial recurrence was distant. CONCLUSIONS: The most likely explanations for the lack of efficacy of CAP are poor compliance to the protocol and relative inactivity of the regimen, compared with the activity of drug combinations used in more recent studies. On the basis of this trial, adjuvant therapy with CAP should not be recommended for patients with resected stage I lung cancer. IMPLICATIONS: Further trials to test adjuvant therapy are indicated, but investigators should use better antiemetics to improve patient compliance as well as more active chemotherapy regimens.
Aged↗
Expression patterns of immediate early transcription factors in human non-small cell lung cancer. The Lung Cancer Study Group.
In 1995, there will be 172,000 new cases of lung cancer diagnosed and 153,000 deaths from this disease in the United States. While the pathogenesis of the disease process is poorly understood, a growing body of evidence suggests that abnormalities in cellular regulatory genes may play an important role in the induction, maintenance and/or progression of some tumor types. These genes include both growth promoting oncogenes as well as growth inhibitory or suppressor genes. Included among these genetic sequences are several cellular transcription factors. A group of these factors including c-jun, c-fos and EGR1 are members of a class of genes known as immediate early genes whose expression are inducible by a variety of stimuli including mitogenic and differentiation inducing growth factors, indicating a potential important role for these genes in normal growth processes. Since these genes are involved in early regulation of cellular growth properties and at least two (c-jun and c-fos) can act as oncogenes, we wished to determine whether their expression levels were altered in human non-small cell lung cancers (NSCLC) compared to normal lung tissue. To address this, Northern blot analyses were performed using c-fos, c-jun and EGR1 probes on RNA extracted from 101 NSCLC tumor specimens and adjacent uninvolved lung tissue. Analysis of this cohort revealed that 72% of the normal tissues demonstrate significantly greater expression of these transcription factors as compared to adjacent malignant tissue. Moreover, this expression pattern appeared to be coordinate for all three genes in the majority of cases. This differential expression pattern was confirmed at the protein level using an immunohistochemical approach with antibodies directed against the c-jun, c-fos and EGR1 gene products. Southern blot analyses demonstrated no gross alterations of these sequences at the DNA level, indicating that the observed differential expression pattern was not due to gross structural changes in the genes. These data suggest that down-regulation of these genes may be involved in the pathogenesis of lung cancer.
Base Sequence↗
Should subcarinal lymph nodes be routinely examined in patients with non-small cell lung cancer? The Lung Cancer Study Group.
This study is based on a retrospective analysis of 163 patients with stage III non-small cell lung cancer randomized to one of three Lung Cancer Study Group postoperative resection-adjuvant treatment protocols. All patients underwent rigorous surgical/pathologic staging including required removal and examination of bronchopulmonary, hilar, subcarinal, and paratracheal lymph nodes. Patients were grouped as follows: group I, only subcarinal nodes diseased (N = 40); group II, only high paratracheal nodes diseases (N = 32); group III, only mid-mediastinal nodes diseased (N = 48); and group IV, subcarinal nodes plus nodes from any other site diseased (N = 43). Patient deaths and tumor recurrences were recorded. The death rate was highest for patients with metastases to subcarinal nodes plus nodes in another site (group IV). Pairwise comparisons of the survival rates of patients in each group disclosed a significant difference between group III and IV (p less than 0.02). In view of this observation, the Lung Cancer Study Group recommends that all patients have rigorous mediastinal lymph node staging done at the time of pulmonary resection to establish prognosis and criteria for study of adjuvant treatment interventions.
Carcinoma, Non-Small-Cell Lung↗
Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. The Lung Cancer Study Group.
Mutations that prevent the normal expression of the retinoblastoma susceptibility gene (RB) have been linked to the pathogenesis of several human malignancies. Mutational inactivation of this tumor-suppressor gene appears to initiate the development of retinoblastoma, and may also contribute to the pathogenesis of osteosarcomas, soft-tissue sarcomas, small-cell lung cancer and other malignancies. In cooperation with the Lung Cancer Study Group, we studied the structure and expression of the RB gene in a cohort of 219 primary non-small-cell lung cancers (NSCLCs). RB gene structure was studied at the DNA level by Southern blot and chromosome 13 restriction fragment length polymorphism analyses. Expression of the RB gene was evaluated by Northern analysis of the transcript and immunohistochemical analysis of the protein (p105RB). Immunohistochemistry of the RB protein proved to be the most sensitive method for the detection of Rb gene inactivation. Absent or abnormal RB protein staining was detected in 53/163 (32%) evaluable cases studied, while Northern analysis showed 22/219 cases to have an altered or absent RB transcript. Southern analysis revealed only two cases of structural alteration of the gene, but loss of heterozygosity from chromosome 13 was common in tumors that failed to express the protein. Analysis of the clinical outcomes of the patients whose tumors were studied did not show any correlation of RB inactivation with time to relapse or death. The data from this study indicate that the RB gene is inactivated in a significant number of NSCLCs. The role that these mutations may play in the development of NSCLC remains to be defined.
Base Sequence↗
Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer. Fukuoka Lung Cancer Study Group.
PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. METHODS: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.
Aged↗
The use of gemcitabine in non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group. Provincial Systemic Treatment Disease Site Group.
GUIDELINE QUESTION: Is there a role for the use of gemcitabine in the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)? OBJECTIVE: To make recommendations about the use of gemcitabine in the management of medically appropriate patients with stage IIIB-IV NSCLC. OUTCOMES: The outcomes of interest were survival, response rate, symptomatic response, response duration and toxicity. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Lung Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The practice guideline report was reviewed by the Provincial Lung Cancer DSG and by the Systemic Treatment Disease Site Group. These committees comprise medical and radiation oncologists, surgeons, pathologists, nurses, a psychologist, a medical sociologist and administrators. One community representative participated in the development of this practice guideline. QUALITY OF EVIDENCE: Five phase II studies of single-agent gemcitabine in advanced NSCLC were reviewed. Four of these are published as full reports. Two randomized phase II studies comparing single-agent gemcitabine with etoposide plus cisplatin were also reviewed. One of these studies is fully published. Seven phase II studies of gemcitabine in combination with cisplatin and I phase II study of gemcitabine in combination with ifosfamide were reviewed. Three randomized controlled trials (RCTs) and 1 randomized phase II study, published in abstract form, compared gemcitabine combination chemotherapy with cisplatin combination chemotherapy. An additional phase II study, published in abstract form, of gemcitabine as salvage therapy in previously treated patients was also included. BENEFITS: Four phase II studies of single-agent gemcitabine at a dose of 1000 mg/m2 or more showed a combined response rate of 19% (intention-to-treat analysis; 95% confidence interval [CI] 15% to 24%) or 21% (efficacy analysis; 95% CI 17% to 26%) in advanced NSCLC. Median survival ranged from 7 to 9 months. Improvement from baseline in cough, hemoptysis and dyspnea was comparable to what would be expected with radiation therapy and with standard combination chemotherapy regimens. Improvement from baseline in their performance status was reported in 52% of treated patients. The 2 randomized phase II studies reported equivalent response rates for gemcitabine compared with etoposide plus cisplatin; the response data were pooled, which resulted in a nonsignificant benefit for gemcitabine (common odds ratio [OR] 0.90; 95% CI 0.43 to 1.90; p = 0.78). Gemcitabine has most frequently been combined with cisplatin, yielding a combined response rate of 44% (intention-to-treat; 95% CI 36% to 47%) or 45% (efficacy; 95% CI 39% to 51%) from 7 phase II studies. Median survival times ranged from 10 to 14 months. One phase II randomized study compared gemcitabine-cisplatin-vinorelbine vs. cisplatin-epirubicin-vindesine plus lonidamine and demonstrated a higher response rate (62% vs. 35%) in favour of the gemcitabine combination. Three RCTs demonstrated increased response rates for the combination of gemcitabine-cisplatin over either cisplatin alone or other combination regimens [(gemcitabine-cisplatin 35% vs. etoposide-cisplatin 12%; p = 0.001), (gemcitabine-cisplatin 31% vs. cisplatin 9%; p = 0.0001), (gemcitabine-cisplatin 40% vs. mitomycin, ifosfamide, cisplatin 28%; p = 0.03)]. HARMS: The major dose-limiting toxicity is neutropenia. Despite this, infection rates are low. Significant adverse effects that have an impact on the patient's quality of life or require the discontinuance of treatment are reported to be less than with any other single agent or combination of agents. Grade 3 or 4 dyspnea has been reported to occur in fewer than 2% of cases and may be drug related. (ABSTRACT TRUNCATED)
Antimetabolites, Antineoplastic↗
Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.
PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.
Adult↗
Unresected stage III non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group.
GUIDELINE QUESTIONS: 1) What is the role of different schedules or doses of radiotherapy in patients with unresected, clinical or pathological, stage III non-small-cell lung cancer (NSCLC)? 2) Does chemotherapy combined with radiotherapy provide improved survival compared with radiotherapy alone in patients with unresected NSCLC? OBJECTIVE: To make recommendations about the role of chemotherapy and radiotherapy in the treatment of unresected stage III NSCLC. OUTCOMES: Survival is the primary outcome of interest. Quality of life is a secondary outcome. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 5 members of the Provincial Lung Cancer Disease Site Group (Lung DSG) of the Ontario Cancer Treatment Practice Guidelines Initiative. The Lung DSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologist and a medical sociologist. No community representative participated in the development of this guideline. QUALITY OF EVIDENCE: Two meta-analyses were available for review. The specific analysis of interest examined the role of combined chemotherapy plus radiotherapy v. radiotherapy alone in locally advanced disease. The first meta-analysis included combined data from 22 randomized controlled (RCTs) involving a total of 3033 patients. The second included combined data from 14 RCTs involving a total of 2589 patients. Also reviewed were 4 RCTs of radiotherapy alone, 1 trial of combined chemotherapy and radiotherapy that was not included in the meta-analysis, 4 abstracts of studies of combined chemotherapy and radiotherapy, and 4 trials examining the role of hyperfractionated radiotherapy. BENEFITS: In the first meta-analysis, an overall benefit was detected at 2 years for the use of combined chemotherapy and radiotherapy. A hazard ratio of 0.90 (p = 0.006), or a 10% reduction in the risk of death, translated into an absolute benefit of 3% at 2 years and 2% at 5 years. A subgroup analysis of cisplatin-based chemotherapy plus radiotherapy versus radiotherapy alone demonstrated a 13% reduction in the risk of death in the combined treatment arm (pooled hazard ratio 0.87, 95% confidence interval [CI] 0.79-0.96), for an absolute benefit of 4% at 2 years. In the second meta-analysis, there was a 13% reduction in the risk of death in the combined therapy arm at 2 years (pooled relative risk [RR] 0.87, 95% CI 0.81-0.94) and a 17% reduction at 3 years (pooled RR 0.83, 95% CI 0.77-0.90). Subgroup analysis of cisplatin-based chemotherapy plus radiotherapy versus radiotherapy alone showed similar results: a 15% reduction in the risk of death in the combined therapy arm at 2 years (pooled RR 0.85, 95% CI 0.79-0.92) and a 19% reduction at 3 years (pooled RR 0.81, 95% CI 0.74-0.88). PRACTICE GUIDELINE: For patients with unresected stage III NSCLC, the combination of cisplatin-based chemotherapy and radical radiotherapy provides a survival benefit compared with radiotherapy alone. This guideline is based on high-quality evidence from 2 meta-analyses of RCTs. Patients with good performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) and minimal weight loss (less than 5% in the preceding 3 months) have been shown to have a survival benefit from treatment with combined chemotherapy and radiotherapy and should be considered for this type of treatment approach (see section V). For these patients, thoracic irradiation of 60 Gy in 30 fractions over 6 weeks, in combination with cisplatin-based chemotherapy, should be recommended as a treatment option. The patient and physician should discuss fully the benefits, limitations and toxic effects of therapy. Patients not meeting these criteria are not candidates for combined therapy; those experiencing symptoms amenable to treatment should receive palliative thoracic irradiation. At this time, hyperfractionated radiotherapy is not recommended outside of the context of a clinical trial. (ABSTRACT TRUNCATED)
Antineoplastic Agents↗
Genetic susceptibility to lung cancer.
Lung cancer is the most common cause of cancer death in the world. Environmental factors, particularly cigarette smoking, are of paramount importance in determining lung cancer risk. Lung cancer and chronic obstructive lung disease are likely to share some common susceptibility genes, but these have not yet been identified. Evidence from various sources, including twin studies, segregation analyses, and case-control studies, support a heritable component to lung cancer risk in humans. As with many common diseases, susceptibility genes for lung cancer appear to be of low penetrance. Family studies of lung cancer susceptibility using linkage analysis and positional cloning have not been reported; however, a consortium is currently carrying out such studies, and results may soon be available. Association studies support lung cancer risk being partly determined by genes that control the metabolism of carcinogens found in tobacco smoke, with the heritable effects being most prominent in smokers with shorter smoking histories. Of these, the CYP1A1 and GSTM1 polymorphisms have been most consistently implicated. In the mouse, an oligonucleotide repeat polymorphism within an intron of the Ki-ras oncogene is the major lung cancer susceptibility locus; however this locus is not clearly involved in susceptibility to lung cancer in the human. Further understanding of the genetic basis of lung cancer susceptibility has many important implications, ranging from targeting prevention and screening efforts to the most highly susceptible population to developing novel chemopreventive therapies.
Journal Article↗
Phase II study of ACNU as second-line treatment in small-cell lung cancer. EORTC Lung Cancer Cooperative Group.
A total of 24 patients presenting with small-cell lung cancer either resistant to or relapsing within 3 months after first-line treatment were entered in a phase II study of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU). ACNU was given i.v. at a dose of 75 mg/m2 every 6 weeks. We observed a partial response of 7 months' duration in one patient and one case of stable disease that lasted for 6 months; all other subjects exhibited progressive disease. Two patients developed brain metastases during treatment. The toxicity of ACNU consisted mainly of bone marrow suppression, especially thrombocytopenia. At this dose and on this schedule, ACNU shows minimal activity as second-line treatment in small-cell lung cancer.
Carcinoma, Small Cell↗