PubMed Health⌕ Search

Biomedical subjects

F A Shepherd

Publications and source records attributed to F A Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1999

The influence of age on the delivery, tolerance, and efficacy of thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer.

PURPOSE: To assess the impact of age on the delivery, tolerance, and efficacy of thoracic irradiation (TI) for limited small cell lung cancer (L-SCLC). METHODS AND MATERIALS: This is a retrospective review of data from 608 patients 80 years or less with L-SCLC, who participated in two previously reported randomized trials (BR3 and BR.6) of the National Cancer Institute of Canada. All patients received the same chemotherapy, consisting of cyclophosphamide, doxorubicin, vincristine (CAV), and etoposide cisplatin (EP) delivered either in sequential or alternating sequence. In BR.3, TI was given after chemotherapy with randomization to 25 Gy in 10 fractions or 37.5 Gy in 15 fractions. In BR.6, TI (40 Gy in 15 fractions) was given concurrently with EP with randomization to either the early (with cycle 2, week 4) or late (with cycle 6, week 16) arm. RESULTS: A total of 665 patients entered these two trials. Of these, 608 patients were eligible for analysis, 300 in BR.3 and 308 in BR.6. Five hundred and twenty patients were under age 70 and 88 patients were 70 years or older. Baseline characteristics between the two groups were comparable. In BR3, 179 patients (60%) participated in radiotherapy randomization (61% young, 52% elderly), and 176 patients actually received TI. In BR.6, randomization occurred at study entry for all patients, and 282 (91.6%) patients received TI (92% young, 88% elderly). More patients of both age groups randomized to receive late TI did not receive TI (13% and 14%) than those randomized to the early TI arm (3%) of BR.6. We could identify no tendency to reduce field sizes to minimize toxicity in either age group at higher doses of TI. Once TI was started, there was no difference between the two age groups with regards to the proportion of patients who completed TI, although elderly patients were less likely to complete high dose TI. Of those who completed TI, there was no difference in the time to complete TI, mean dose delivered or in the incidence of acute and late TI-related toxicities. No statistical difference in response rate, local relapse rate, or overall survival was seen between young and older age groups. CONCLUSION: In summary, in the dose range examined, age does not appear to impact on the delivery, tolerance or efficacy of TI in the combined modality management of L-SCLC. Potentially curative combined modality treatment should not be withheld on the basis of age.

Age Factors↗
PubMed1999

Detection of occult low-grade b-cell non-Hodgkin's lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia.

Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and has been shown to be associated with the benign lymphoproliferative disorder, mixed cryoglobulinemia (MC). Preliminary studies suggest that there may be an association between chronic hepatitis C, MC, and non-Hodgkin's lymphoma (NHL). The aim of this study was to determine whether patients with chronic HCV and MC have occult bone marrow NHL. Sixteen patients with chronic HCV and clinically active MC underwent bone marrow biopsy and aspiration. Flow cytometry was performed looking for abnormal B-cell lineage. Molecular genetic studies were performed to identify B-cell monoclonality. Nine of 16 patients (56%) had abnormal marrow morphology, 7 (44%) were interpreted as suspicious for lymphoma, and 2 (13%) as consistent with lymphoma. Flow cytometry on 13 patients identified 5 (39%) with increased B-cell populations. Molecular analysis on 13 patients identified 3 (23%) with monoclonal proliferation of the B-cell lineage. All 13 patients tested for Epstein-Barr virus were negative by polymerase chain reaction (PCR). Four of 16 patients (25%) had marrow morphology and evidence of a monoclonal B-cell population by flow cytometry and/or molecular studies, consistent with B-cell NHL. These findings confirm the presence of lymphoproliferative disorders in patients with chronic HCV and MC. Some of these disorders meet the morphological and molecular criteria for the diagnosis of malignant lymphoma.

Adult↗
PubMed1999

Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.

PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.

Antineoplastic Agents↗
PubMed1999

Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. RESULTS: Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P =.043). Significant factors for survival were tumor stage (P =.0021); weight loss (P =. 013); and high tumor cell expression of MMP-3 (P =.077), MMP-11 (P =. 031), and MMP-14 (P =.019). MMP and TIMP expression did not differ significantly between stages. CONCLUSION: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.

Carcinoma, Small Cell↗
PubMed1999

Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Chemotherapy for non-small cell lung cancer: have we reached a new plateau?

The last decade has seen the introduction of several new chemotherapeutic agents that have activity against non-small cell lung cancer (NSCLC) and produce single-agent response rates of > or = 20% in previously untreated patients with advanced tumors. Furthermore, the results of phase I-II trials have shown that the agents can be combined safely with cisplatin or carboplatin and that most combinations result in response rates of 35% to 40% or more. Gemcitabine, paclitaxel, vinorelbine, and tirapazamine have all been studied in combination with cisplatin in trials that compared the combinations with cisplatin alone. All trials reported response rates that were significantly higher for the combination arm and, with the exception of the paclitaxel trial, median and 1-year survival rates were also significantly greater. Vinorelbine as a single agent was compared with vinorelbine in combination with cisplatin in three studies. Although response and survival rates were longer for the combination arms, single-agent vinorelbine produced median survivals of longer than 30 weeks in all trials and a 1-year survival rate of 30% in one study. Single-agent gemcitabine was compared with the combination of etoposide and cisplatin in two trials. In each study, the response to gemcitabine was equal to that of the combination arm, and the 1-year survival rate was actually superior for the single-agent gemcitabine arm. Combinations of the new agents with cisplatin or carboplatin also have been evaluated in randomized phase III trials and compared with standard chemotherapy regimens for the treatment of NSCLC. The vinorelbine/cisplatin combination was found to be superior to vindesine/cisplatin. Paclitaxel/cisplatin and gemcitabine/cisplatin were both found to be superior to etoposide/cisplatin. Survival gains have been modest, with median survival ranging from approximately 8 to 10 months and 1-year survival rates with the new regimens ranging from 32% to 41%. The new chemotherapy regimens have resulted in modest benefit and have set a new standard for the treatment of advanced NSCLC.

Antineoplastic Agents↗
PubMed1999

Lymphoma of the gastrointestinal tract.

Non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract accounts for 4% to 20% of all NHLs and is the most common extranodal site of presentation. The stomach is the major organ involved by GI lymphoma. Helicobacter pylori infection, immunosuppression after solid-organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus (HIV) infection may be risk factors for GI lymphoma. A significant proportion of gastric lymphomas are of low-grade histology and arise from mucosal-associated lymphoid tissue (MALT). Such MALT lymphomas may be associated with H. pylori infection and may undergo complete regression following eradication of H. pylori. Lymphoma of the small bowel, colon, and rectum may also occur, but are less common than gastric lymphoma. Distinct clinicopathologic entities, such as primary intestinal T-cell lymphoma, immunoproliferative small intestinal disease, and multiple lymphomatous polyposis have been described. Surgery, radiation therapy, and chemotherapy have been used in the treatment of GI lymphomas. However, the optimal management of these lymphomas has never been determined by prospective randomized clinical trials. Such trials by cooperative groups are needed to answer many of the vital unanswered questions concerning extranodal lymphomas of the GI tract.

Gastrointestinal Neoplasms↗
PubMed1998

Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study.

Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment.

Adult↗
PubMed1998

Safety of therapeutic anticoagulation in patients with multiple myeloma receiving autologous stem cell transplantation.

The use of autologous stem cell transplantation (ASCT) for the treatment of multiple myeloma is increasing. Anticoagulation may be required during ASCT for conditions such as Hickman line thrombosis. The safety of anticoagulation in patients receiving ASCT is unknown. We report a retrospective case-control study of the safety of therapeutic anticoagulation in patients with multiple myeloma receiving ASCT. We identified 10 patients who received therapeutic anticoagulation during ASCT. For each of the 10 cases identified, two matched controls were selected. As a primary endpoint, bleeding complications were assessed. Secondary endpoints included survival, length of hospital stay, transfusion requirements, grade 4 toxicity, and days to platelet engraftment. Bleeding complications were not significantly different between patients receiving anticoagulation and controls (P = 0.3). Three of 10 anticoagulated patients and two of 20 controls had a bleeding complication. Mortality during admission was similar (P = 1.0); one anticoagulated patient and one control died of sepsis. A trend towards increased median number of platelet transfusions in the heparinized patients was seen (27 vs 12 units, P = 0.055), reflecting the higher transfusion threshold chosen for the anticoagulated patients. The other secondary endpoints did not differ between patients and controls. In this case control study, bleeding was not significantly increased in the group receiving anticoagulation during ASCT. This group electively received more units of platelets than controls. Thus, therapeutic anticoagulation can be managed with minimal increased toxicity during ASCT.

Adult↗
PubMed1998

Lymphoproliferative disorders after lung transplantation: imaging features.

PURPOSE: To define the imaging features of lymphoproliferative disorders that occur after lung transplantation. MATERIALS AND METHODS: In a retrospective review of the cases of 246 patients who had undergone lung transplantation (62 single- and 184 double-lung transplants) between 1987 and 1997, the authors found nine patients (seven men and two women, aged 16-59 years [mean, 42.2 years]) with posttransplantation lymphoproliferative disorders. All imaging, clinical, and pathologic findings pertaining to these disorders were reviewed. RESULTS: Eight of the nine patients had isolated intrathoracic disease. The most common abnormality (six patients) was the presence of multiple, well-defined pulmonary nodules. These nodules, when multiple, had basilar and peripheral predominance. Other abnormal features included hilar or mediastinal adenopathy (two patients), a consolidated upper lobe (one patient), a pleural mass (one patient), and bulky abdominal lymphadenopathy (one patient with pathologically proved Hodgkin lymphoma). Three patients had nodules with a surrounding area of ground-glass opacity (halo sign), and one patient had multiple ill-defined areas of centrilobular opacity. Air bronchograms were not often seen, and pleural effusions were absent. CONCLUSION: The presence of well-defined pulmonary nodules in a patient who has undergone lung transplantation should raise concern about the possibility of posttransplantation lymphoproliferative disorder. In such cases, performance of pathologic studies should be expedited.

Adult↗
PubMed1998

Economic issues in lung cancer: a review.

PURPOSE: Lung cancer is a major source of morbidity, mortality, and health care costs in the developed and developing world. It is estimated that lung cancer is responsible for 20% of all cancer care costs. Concerns exist that this expenditure is associated with questionable benefits. DESIGN: The economic literature that relates to smoking was reviewed, followed by a summary of the economics of the diagnosis, treatment, and palliation of lung cancer. Methodologic considerations are also discussed in this section. RESULTS: Published studies suggest that the increased lifetime health care costs from smoking-related illnesses in smokers are partially or fully offset by the higher medical costs that result from increased longevity in nonsmokers. However, lost productivity costs, which result from morbidity and early mortality among smokers, result in an overall net cost of smoking to society. Discounting rates of 3% to 5% do not substantively alter these results. The per-patient cost to treat lung cancer is substantial. The major cost center is hospitalization; palliative or terminal treatment is associated with significant costs. Savings can be obtained through the judicious use of diagnostic and staging procedures. Furthermore, combined modality treatment approaches and the palliative use of combination chemotherapy appear to be associated with acceptable cost-effectiveness compared with commonly used therapies for other diseases. CONCLUSION: Although the increased medical care costs of treating smoking-related diseases are somewhat offset by the higher medical care costs due to increased longevity in nonsmokers, the lost productivity that results from smoking results in a net cost to society. Standard approaches to the management of lung cancer are associated with cost-effectiveness similar to that of other commonly used medical interventions.

Canada↗
PubMed1998

Prospective randomized trial of two dose levels of interferon alfa with zidovudine for the treatment of Kaposi's sarcoma associated with human immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study.

PURPOSE: Interferon alfa alone has shown antitumor activity against Kaposi's sarcoma (KS), and phase I and II clinical trials showed that interferon and zidovudine could be administered safely to patients with human immunodeficiency virus (HIV)-associated KS. These observations led to our trial of zidovudine with two dose levels of interferon alfa. METHODS: HIV-positive patients with KS were eligible if they were older than 18 years of age, had a performance status of 0 to 2, and were free of active infection. All patients received zidovudine 500 mg daily and were randomized to receive-interferon alfa 1 million U or 8 million U subcutaneously daily. RESULTS: The 108 eligible and assessable patients were well balanced for known prognostic factors. Response was reported in 31% of high-dose therapy and 8% of low-dose therapy patients (P=.011). Response at both dose levels was higher for patients with CD4 counts greater than 150 x 10(9)/L. The median time to progression was longer for patients in the 8-million U arm (18 v 13 weeks; P=.002). Both hematologic and nonhematologic toxicities were higher in the high-dose arm; 50 of 54 patients who received 8 million U required dose alterations in the first 4 months compared with only 19 of 53 patients who received 1 million U (P=.0002). No significant differences were reported with respect to improvement in CD4 count, elimination of p24 antigen, or development of opportunistic infections. CONCLUSION: Zidovudine and moderate-dose-interferon alfa may be combined safely for the treatment of HIV-associated KS, and both response to treatment and toxicity are dose related.

Adult↗
PubMed1998

Ifosfamide and paclitaxel combinations for the treatment of advanced non-small cell lung cancer.

Ifosfamide and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are among the most active agents for the treatment of non-small cell lung cancer, with single-agent response rates of 20% or greater in previously untreated patients with advanced disease. These two agents have been evaluated in several phase I and II trials of two-, three-, and four-drug regimens to determine their safety and efficacy in this patient population. Ifosfamide and paclitaxel doublets were evaluated in two phase I and II trials. Response rates ranged from 15.4% to 34%, with 1-year survival rates as high as 37%. Toxicity was acceptable, with greater degrees of myelosuppression seen with 24-hour infusion times for paclitaxel. Three-drug studies of ifosfamide, paclitaxel, and a platinum analogue have shown that these three drugs may be combined. Myelosuppression is considerable, however, and febrile neutropenia rates are high, even when growth factors are used. The addition of etoposide to the three-drug regimens has been evaluated only in phase I studies. Myelosuppression increases, and rates of febrile neutropenia as high as 26% have been reported. The lack of any suggestion of additional efficacy and the substantial toxicity suggest that four-drug combinations are not advisable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Combined cisplatin and gemcitabine for non-small cell lung cancer: influence of scheduling on toxicity and drug delivery.

The scheduling of cytotoxic chemotherapy has important bearing on the toxicity and ability to deliver chemotherapy at or close to full dose. We report new data on the influence of different schedules of cisplatin and gemcitabine on toxicity and drug delivery in phase II studies of non-small cell lung cancer. Patients in six phase II studies had standard entry criteria for advanced non-small cell lung cancer. Whereas gemcitabine was given on days 1, 8, and 15 of a 28-day cycle in all these studies, the scheduling of cisplatin varied and was given either on day 1, day 2, day 15 (in two studies), or days 1, 8, and 15 (in two studies). The protocol dose per infusion for gemcitabine was 1,000 mg/m2 (five studies) and 1,500 mg/m2 (one study); for cisplatin, it was 100 mg/m2 when given once per cycle and 30 mg/m2 when given on days 1, 8, and 15. Similar dose reduction schedules were implemented in the event of grade 3 or higher drug toxicity for all studies except for the day 1 cisplatin study, in which the dose was omitted for grade 2 thrombocytopenia. Nonhematologic toxicity was very low. Hematologic toxicity was moderate, and in patients who developed grade 3 or 4 toxicity, there was no hemorrhage from thrombocytopenia and neutropenic sepsis was rare. The incidence of grade 3 or 4 thrombocytopenia with the day 1, day 2, day 15 (two studies combined), and days 1, 8, and 15 (two studies combined) cisplatin regimens was 50%, 52%, 26%, and 38%. The incidence of grade 3 or 4 neutropenia with these four regimens was 51%, 37%, 56%, and 49%, respectively. Although the hematologic toxicity might appear relatively similar, it represents the toxicity at the administered rather than the intended (protocol) dose, because drug delivery was reduced or omitted in the event of grade 3 or 4 toxicity. Differences between the schedules are revealed by analysis of the actual dosages delivered. The median dosage of gemcitabine per scheduled infusion was statistically higher with the day 15 cisplatin regimens (combined) compared with any of the other regimens treating at 1,000 mg/m2 (P < .003, z-score). The dose with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 664, 829, 889, and 774 mg/m2, respectively. Both the percentages of cycles in which gemcitabine infusions were given at full dose and in which there were no omissions of gemcitabine infusions (including infusions with dose reductions) were statistically higher in the day 15 cisplatin regimen than with any of the other regimens (P < .0001, chi-square test). The percentage of cycles containing full-dose gemcitabine with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 24%, 44%, 75%, and 46%, respectively. The percentage of cycles in which there were no omissions of gemcitabine infusions for the four regimens above was 32%, 55%, 83%, and 72%, respectively. Apart from the once-weekly regimen (days 1, 8, and 15) in which the protocol gemcitabine dose was 1,250 mg/m2, the day 15 cisplatin schedule allowed for the highest median concentration of gemcitabine. More importantly, the day 15 cisplatin schedule provided the longest duration of gemcitabine exposure, which is particularly important for its activity as gemcitabine is a phase-specific agent. The day 15 cisplatin schedule is associated with the best dose intensity and the longest median duration of exposure to gemcitabine, and best meets the goal of administering both agents at full doses in combination.

Adult↗
PubMed1997

Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre.

BACKGROUND: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. METHODS: Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. RESULTS: Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. IMPLICATIONS: Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.

Actuarial Analysis↗
PubMed1997

Alternatives to chemotherapy and radiotherapy as adjuvant treatment for lung cancer.

Because adjuvant chemotherapy has resulted in only modest prolongation of survival for patients with lung cancer, investigators have turned to the evaluation of alternative treatment strategies for this patient population. Immunotherapy with Bacillus Calmette Guerin, Corynebacterium parvum, and levamisole has been evaluated in several prospective randomized trials, and no study has shown a statistically significant difference in overall survival. Interferon has been evaluated in three trials of adjuvant therapy after response to chemotherapy for small cell lung cancer. Different interferon preparations were used, but none of the trials showed a significant prolongation of survival. The retinoids have been evaluated as adjuvant treatment after complete resection of stage IN-SCLC. One trial showed a reduction in second primary tumors, and in particular, tumors to tobacco smoking in patients treated with retinyl palmitate. A second trial using 13-cis retinoic acid is ongoing in North America. In the last decade, several inhibitors of angiogenesis have been identified, and they are now beginning to be evaluated in the clinical setting. The National Cancer Institute of Canada Clinical Trials Group and the European Organization for Research and Treatment of Cancer have initiated a study of adjuvant marimastat, a metalloproteinase inhibitor, for patients who have responded to induction chemotherapy for small cell lung cancer. This is the first adjuvant antiangiogenesis factor trial to be initiated for any tumor type. Other investigational agents which are currently undergoing Phase I and Phase II testing include monoclonal antibodies which may inhibit tumour cell growth by binding to growth factors, or which may be conjugated to toxins or chemotherapeutic agents which result in tumour cell death. In the last decade, we have witnessed an explosion in our knowledge and understanding of the regulation of normal and neoplastic cell growth at the molecular level. It remains only speculative at this time as to whether manipulation of abnormal genes in malignant cells will be clinically possible, and whether treatment of this sort may be applied in an adjuvant setting.

Adjuvants, Immunologic↗
PubMed1997

Malignant pericardial effusion.

The clinical symptoms of cardiac tamponade associated with malignancy are reviewed, and the importance of these symptoms in relationship to treatment decisions are discussed. The clinical findings of tamponade and the echocardiographic findings have been correlated. The approach to treatment of cardiac tamponade has been summarized. The various surgical techniques, including pericardial window formation, subxyphoid drainage, and thoracoscopy and video-assisted thoracoscopy, are discussed and the relative benefits of the various procedures have been presented. Results of the less invasive percutaneous balloon pericardiostomy procedure have also been reviewed, and updates of recent small series have been included. Medical management of malignant pericardial effusion with small-bore tube drainage followed by sclerosis has been reviewed, and the results of recent series reporting the effectiveness of various sclerosing agents, including tetracycline, doxycycline, and bleomycin, have been compared.

Cardiac Tamponade↗