Showing papers in "American Journal of Clinical Oncology in 1997"
TL;DR: Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.
Abstract: Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.
130 citations
TL;DR: A case of spontaneous regression of pleural and intrapulmonary metastases from renal cell cancer is reported with more than 60 cases reported since the original review of this clinical phenomenon in 1964.
Abstract: A case of spontaneous regression of pleural and intrapulmonary metastases from renal cell cancer is reported with more than 60 cases reported since the original review of this clinical phenomenon in 1964. The metastatic disease sites are most often pulmonary, but extrapulmonary sites include liver, bone, and CNS regressions. The role of nephrectomy in "spontaneous regression" continues to be obscure, accounting for < 50% of documented cases. Immunologic mechanisms, although intellectually attractive, have not been identified.
126 citations
TL;DR: This series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis and recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.
Abstract: Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a literature review disclosed fewer than 150 cases. SCCP has an aggressive course, and both local and distant failure is common. The optimal treatment method has not been clearly established. We review our experience with 7 patients, with attention paid to clinical and pathological details based on a review of the histological specimens. Three patients had mixed tumors of both SCCP and adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had pure small cell. Our series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis. All patients progressed locally, and at least 5 later developed distant metastases. Treatment with combination chemotherapy and/or hormones resulted in short-lived responses in most patients. We recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.
85 citations
TL;DR: It is concluded that the comeasurement of CA 19-9 and CA-50, and to some degree of CEA, is justifiable for gastric cancer and may be useful for early detection of recurrence after curative surgery and adjuvant chemotherapy.
Abstract: This study was conducted to investigate the clinical utility of CEA, CA 19-9, and CA-50 in the diagnosis, monitoring, and prognosis of 62 gastric carcinoma patients having either adjuvant or palliative chemotherapy. Patients were divided in two groups: group A included patients treated on an adjuvant basis following a curative resection of gastric cancer, and group B included patients with residual disease post surgery or patients with inoperable tumor or generalized disease. Serum marker levels were measured in a prospective study just before the initiation of chemotherapy and before each course during chemotherapy. In group A, CEA was positive in 2/25 (8%) patients, CA 19-9 in 1/25 (4%), and CA-50 in 1/25 (4%). In group B the sensitivity of CEA was 48.6% (18/37 patients), of CA 19-9 64.9% (27/37 patients), and of CA-50 70.3% (26/37) patients. There was a significant correlation between the CA 19-9 and CA-50 levels in both groups. No correlation was found between the sensitivity or the absolute initial marker levels and the tumor's differentiation or extent of disease. In group A the only patient with initially elevated CA 19-9 and CA-50 values relapsed early while he was on adjuvant chemotherapy. It was also found that the rising final CA 19-9 and CA-50 values at the end of chemotherapy were correlated with an increased incidence of relapse, but not with the disease-free interval. In group B the initially low marker levels showed a trend to predict a favorable outcome of treatment. There was no statistically significant correlation between the marker titers before each course and response to chemotherapy. It is concluded that the comeasurement of CA 19-9 and CA-50, and to some degree of CEA, is justifiable for gastric cancer. The estimation of CA 19-9 and CA-50 may be useful for early detection of recurrence after curative surgery and adjuvant chemotherapy. In advanced or recurrent gastric cancer, the estimation of either CA 19-9 or CA-50 and CEA serum values may help in checking the prognosis, determining the efficacy of palliative treatment modalities, and recognizing recurrences.
83 citations
TL;DR: Fenretinide (N-4-hydroxyphenyl retinamide) (4HPR) has been found to be relatively nontoxic in preclinical experiments and early clinical trials, and its toxicity and feasibility for use as a chemoprevention agent in men at high risk for prostate cancer was evaluated in this study.
Abstract: Prostate cancer is the most common cancer diagnosed in American men. The need to find effective means of preventing this disease is clear. Vitamin A and its analogues (retinoids) act as transcriptional regulators within the nucleus and have been tested as both preventative and therapeutic agents in human malignancy. Fenretinide (N-4-hydroxyphenyl retinamide) (4HPR) has been found to be relatively nontoxic in preclinical experiments and early clinical trials. Its toxicity and feasibility for use as a chemoprevention agent in men at high risk for prostate cancer was evaluated in this study. Twenty-two patients were entered into a clinical trial that involved taking 4HPR for twelve 28-day cycles. Eight patients with negative prestudy biopsies had positive prostate biopsies prior to or at the time of their 12th cycle evaluation. This led to early closure of the study. 4HPR was well-tolerated, and no major toxicities were associated with its use. The significance of this study is limited due to small sample size. Chemoprevention studies such as this can be difficult to complete because of the commitment required of otherwise healthy individuals; nevertheless additional dosages and schedules for 4HPR administration merit further investigation.
67 citations
TL;DR: ABVD is associated with relatively better preservation of gonadal function and three patients treated with ABVD fathered children post-therapy.
Abstract: To assess the effect of combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on gonadal function in patients treated for Hodgkin's disease, we assessed 38 male patients with Hodgkin's disease who were >15 years of age and in complete remission for the development
67 citations
TL;DR: SRT combined with CDDP is safe, with durable responses in some patients, and further investigations to determine optimal SRT and CDDP doses and scheduling are justified.
Abstract: External beam irradiation of malignant astrocytoma often provides temporary local tumor control, but dose is limited by potential toxicity to normal brain. Fractionated stereotactic radiotherapy (SRT) provides additional radiation to the tumor with less dose deposition in adjacent normal brain. We administered a potential radiosensitizer, cis-platinum (CDDP), to optimize the therapeutic index. CDDP (40 mg/m2) was given weekly, with SRT once or twice weekly, to 20 patients. One had a partial response, 11 stable disease, and eight progressed despite therapy. Acute toxicities were manageable. Five patients required surgery for tumor progression or radiation necrosis. Median response duration was 18.5 weeks and median survival was 55 weeks. SRT combined with CDDP is safe, with durable responses in some patients. Further investigations to determine optimal SRT and CDDP doses and scheduling are justified.
62 citations
TL;DR: Radiation therapy may be of benefit in palliating DEB patients who have locally advanced carcinoma, but has been associated with enhanced normal tissue toxicity, suggesting a narrow or absent therapeutic index between irradiated carcinoma and skin.
Abstract: Dystrophic epidermolysis bullosa (DEB) is a debilitating systemic disease frequently associated with biologically aggressive secondary squamous cell carcinomas arising from affected skin or mucosal surfaces. Treatment of these carcinomas with surgery, chemotherapy, or radiation is complicated by inherently poor wound healing. We report on two DEB patients treated with radiation therapy for locally advanced squamous cell carcinoma, and retrospectively analyze 10 DEB patients treated with radiation, reported in the literature. Of the 11 fully available and described case results from radiation therapy, six (54%) patients demonstrated a partial tumor response. All patients receiving > 4,500 cGy developed moist skin desquamation and delayed skin healing. Radiation therapy may be of benefit in palliating DEB patients who have locally advanced carcinoma, but has been associated with enhanced normal tissue toxicity, suggesting a narrow or absent therapeutic index between irradiated carcinoma and skin.
55 citations
TL;DR: The tobacco nonuser who develops SCHNC is likely to be female and white and to have a primary tongue cancer, and a significant association with environmental tobacco smoke exposure is suggested by the data.
Abstract: Tobacco and alcohol abuse are the major known risk factors for the development of squamous cell head and neck cancer (SCHNC). Information about this disease in nonsmokers, however, is limited. We retrospectively studied a group of 59 tobacco nonusers with SCHNC, diagnosed since 1986 at the Cleveland Clinic Foundation (CCF). Two objectives were defined: (a) to characterize this nonsmoking population of patients and identify any significant differences compared with a control population consisting of all patients diagnosed with SCHNC at the CCF between 1986 and 1993 and (b) to determine the prevalence of exposure to environmental tobacco smoke in this nonsmoking group of patients with SCHNC and compare it with the environmental tobacco-smoke exposure in a second, control population of non-SCHNC, nonsmoking patients matched for age, race, sex, and alcohol use. The group of nonsmoking patients with SCHNC was notable for only rare alcohol abuse, a preponderance of whites, and relatively fewer laryngeal primary tumors. There were significantly more women and more tongue primaries. When compared with the control population without cancer, the nonsmoking patients had a significantly higher risk of exposure to environmental tobacco smoke both in the home and in the workplace. We conclude that the tobacco nonuser who develops SCHNC is likely to be female and white and to have a primary tongue cancer. A significant association with environmental tobacco smoke exposure is suggested by our data.
53 citations
TL;DR: Re-irradiation with highly conformal three-dimensional planning provides frequent clinical improvement with acceptable morbidity and should be considered in selected patients with recurrent intracranial neoplasms.
Abstract: We evaluated the potential of three-dimensional conformal therapy for re-irradiation of selected intracranial neoplasms and reviewed the retreatment of 20 patients at the University of Michigan between May 1988 and August 1991. All patients had previously undergone a full course of external beam radiotherapy (RT) to a median dose of 5,940 cGy (range 5,100-6,500 cGy), including five whole brain treatments. All recurrences were unsuitable for brachytherapy or radiosurgery. Various histologies were retreated, including 14 high-grade gliomas. Median time to re-irradiation was 38 months (range 9 months to 19 years, 6 months). RT was delivered with complex plans designed using fully integrated computed tomography/magnetic resonance imaging (CT/ MRI) tumor volume information, and regions of previous parenchymal treatment were avoided if possible. Composite (initial+retreatment) dose-volume histograms (DVH) of dose to nontarget brain allowed comparison of alternative plans to select beam orientations which minimized normal brain irradiation. Mean target dose of re-irradiation was 3,600 cGy (range 3,060-5,940 cGy). Total cumulative dose ranged from 8,060 to 11,940 cGy. Median survival was 9 months, and 1-year actuarial survival was 26%. After retreatment, 8 of 12 patients (67%) had steroid dose decrement and neurologic improvement at 4-48 months (median duration 14 months). Radiographic regression or stabilization of disease was noted in 11 of 16 patients (68%). Re-irradiation with highly conformal three-dimensional planning provides frequent clinical improvement with acceptable morbidity and should be considered in selected patients with recurrent intracranial neoplasms.
53 citations
TL;DR: A case of a 72-year-old women with this highly aggressive malignancy arising from a long-standing lower leg lesion is reported, with widespread metastatic disease 20 months after the diagnosis.
Abstract: Malignant eccrine spiradenoma is an exceedingly rare tumor. A case of a 72-year-old women with this highly aggressive malignancy arising from a long-standing lower leg lesion is reported. Management during the course of disease included surgery, radiation therapy (RT), hyperthermic limb perfusion chemotherapy, and chemotherapy. The patient died of her disease, with widespread metastatic disease 20 months after the diagnosis. A review of the literature is presented, and treatment considerations are summarized.
TL;DR: The treatment resulted feasible on an outpatient basis, with mild toxicity, and ifosfamide appeared less effective than in a previous report at higher doses.
Abstract: We have carried out a phase II study in advanced or metastatic transitional cell carcinoma of the bladder. Eligible patients had unresectable bladder cancer, previously treated with one line of systemic chemotherapy. Treatment consisted of ifosfamide 1000 mg/sm in a 2-hour infusion for 5 consecutive days from d.1 to d.5. Mesna was administered intravenously at a 20% of the ifosfamide dosage before ifosfamide and orally at 40% after 4 and 8 hours from the ifosfamide infusion. Twenty patients entered the study and received a total of 62 cycles: the treatment resulted feasible on an outpatient basis, with mild toxicity. Only one partial response was observed. With this dose and schedule, ifosfamide appeared less effective than in a previous report at higher doses. Toxicity was acceptable.
TL;DR: The results of this study indicate that the schedule of estramustine associated with vinorelbine is active and well tolerated in hormone-refractory prostate cancer patients.
Abstract: Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been reported in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated the activity ofthe following schedule: estramustine, 400 mg/ m 2 orally days 1-42; etoposide, 50 mg/m 2 orally days 1-14; and 28-42; vinorelbine, 20 mg/m 2 days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: median age, 71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients with measurable disease and six patients with bone disease had a partial remission for an overall response rate of 32% (95% confidence interval 15-53%). Seven patients had stabilization of disease and 10 had progression of disease. Median duration of response was 3 months (range 2-5). Prostate-specific antigen in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study indicate that the schedule is active and well tolerated in hormone-refractory prostate cancer patients.
TL;DR: The results of prior studies with human-derived materials in vitro are confirmed, reinforcing the notion that such studies are useful predictors of drug pharmacokinetics and interactions in vivo.
Abstract: This study was performed to evaluate whether concomitant treatment with ketoconazole could reduce the clearance of paclitaxel given to ovarian cancer patients. Paclitaxel, 175 mg/m2, was given as a 3-hour continuous intravenous infusion and repeated every 21 days. Initially, ketoconazole, 100 to 160
TL;DR: Prophylactic treatment against such recurrence in the central nervous system (CNS) was observed, and it may be necessary to improve the treatment outcome of patients with testicular NHL.
Abstract: Non-Hodgkin's lymphoma (NHL) of the testis is a rare disease, and treatment outcome is generally poor. In this retrospective study, we investigated treatment results for testicular NHL in an attempt to develop an effective treatment policy for this disease. The survival rate and characteristics were retrospectively analyzed in eight patients with NHL of the testis who were treated between 1969 and 1991 at Kyoto University Hospital, Department of Radiology. Four patients were at stage IEA, one at stage IIEA, and three at stage IVEA. Of the eight testicular lymphomas, six were classed as intermediate grade lymphomas and two as high-grade lymphomas according to the Working Formulation. All of the eight patients received orchiectomy. Six patients received combined chemotherapy and radiation therapy as the primary treatment for the disease. One patient each was treated with radiation therapy alone or combination chemotherapy alone. The 5-year overall and disease-free survival rate was 45 and 33%, respectively. Even though almost all of the patients had received combination chemotherapy, high incidence of relapse in the central nervous system (CNS) was observed. Prophylactic treatment against such recurrence may be necessary to improve the treatment outcome of patients with testicular NHL.
TL;DR: Recognition of the association between subcutaneous panniculitis and pancreatic neoplasm may prevent long delays in the diagnosis and treatment of this malignancy.
Abstract: Acinar cell carcinoma (ACC) of the pancreas is a rare malignancy accounting for < 1% of pancreatic neoplasms. We report the clinical and biological characteristics of this carcinoma from two cases that were of interest because of their similar presentation: extensive subcutaneous fat necroses from excessive lipase production by these tumors. Immunohistochemical and ultrastructural analyses of both tumors were consistent with an acinar cell line origin. Recognition of the association between subcutaneous panniculitis and pancreatic neoplasm may prevent long delays in the diagnosis and treatment of this malignancy.
TL;DR: It is concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.
Abstract: The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short-term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from short-term cultures. Twenty-four patients with MDR(-) and seven with MDR +(++) were available for survival analysis. Median survival for MDR (-) patients was 10 months, whereas for MDR +(++) patients it was 2 months. This was statistically significance (p < 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.
TL;DR: Because of the lack of cross-resistance to other drugs and the potential synergistic antineoplastic activity, gallium nitrate and hydroxyurea should be further evaluated in combination with other chemotherapeutic agents.
Abstract: Based on preclinical studies demonstrating synergy between gallium and hydroxyurea, we evaluated the efficacy and toxicity of continuous intravenous gallium nitrate in combination with oral hydroxyurea in patients with refractory non-Hodgkin's lymphoma. Fourteen patients, median age 64 years (range 53-89), with stage III or IV low- or intermediate-grade lymphoma were treated with gallium nitrate and hydroxyurea in combination for 7 days at four different dose levels: (a) gallium nitrate, 200 mg/m2/day; hydroxyurea, 500 mg/day; (b) gallium nitrate, 250 mg/m2/day; hydroxyurea, 1,000 mg/day; (c) gallium nitrate, 300 mg/m2/day; hydroxyurea, 1,000 mg/day; and (d) gallium nitrate, 350 mg/m2/day, hydroxyurea, 1,000 mg/day. All patients had progressive disease and had been heavily pretreated. Six of 14 patients had objective tumor regression following treatment (one complete response, one near-complete response, and four partial responses) with a median duration of response of 7 weeks (range 3-38 weeks). An additional four patients had minor responses. Responses occurred at all dose levels and in both low- and intermediate-grade histologic subtypes. The predominant toxicities encountered were anemia and reversible nephrotoxicity. Combination gallium nitrate and hydroxyurea has significant activity in lymphoma and is well tolerated even by elderly patients. Because of the lack of cross-resistance to other drugs and the potential synergistic antineoplastic activity, gallium nitrate and hydroxyurea should be further evaluated in combination with other chemotherapeutic agents.
TL;DR: It is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis.
Abstract: Therapeutic application of immunoglobulin is reported to be successful in radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of prophylactic application of immunoglobulin was investigated. In 42 patients with head and neck cancer, postoperative radiation treatment or radiation combined with chemotherapy was performed. In 20 consecutive patients, prophylactic mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1 ml/day). The 22 following patients received, supplementary to panthenol and nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During the treatment time, the degree of mucositis was examined 3 times a week. The distribution of maximal mucositis degree revealed slightly more severe mucous membrane reaction in the control group compared with the immunoglobulin group (n.s.). The analysis of mean mucositis degrees in both groups demonstrated statistically significant differences (t test, p = 0.031) related to the entire group (n = 42) and to those 16 patients receiving radiation combined with chemotherapy. There was no significant immunoglobulin-induced effect on mucositis in patients treated by radiation alone. The time from the beginning of therapy to the first interruption could be prolonged 5 days in the immunoglobulin group (n.s.). In conclusion, it is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis. In comparison to the published data about therapeutically given immunoglobulin, the clinical efficacy of the prophylactic application of immunoglobulin as it is performed in this study is less evident.
TL;DR: Observation of 15 brain tumor patients indicated that in large brain tumors, the BCB was seriously damaged; in small tumors,the BCB would gradually open; it is thus advisable to give chemotherapy only after 20 Gy of irradiation.
Abstract: Effect of irradiation on blood-cerebrospinal fluid (CSF) barrier (BCB) was studied quantitatively by observing the effect of methotrexate (MTX) permeation into the CSF before, during, and after brain irradiation after i.v. injection of MTX. Observation of 15 brain tumor patients indicated that in large brain tumors, the BCB was seriously damaged; in small tumors, the BCB would gradually open. Compared with the findings before irradiation, the increase of permeability of MTX was zero to threefold. It is thus advisable to give chemotherapy only after 20 Gy of irradiation.
TL;DR: The results of the study suggest that the therapeutic outcome in SCLC with the brain as the single site of metastases at initial diagnosis is similar to that of limited-stage SCLCs.
Abstract: To study the therapeutic outcome of patients with extensive small-cell lung cancer (SCLC) with the brain as the single site of metastases at initial diagnosis, we retrospectively reviewed the outcome of 30 such patients (23 men and seven women; median age, 59 years; range, 36-74 years). Medical histories were taken, and physical examination, complete blood cell count, chemistry profile, chest radiography, radionuclide bone scan, computed tomography (CT) scan of the abdomen or radionuclide liver scan, and CT scan of the head were performed as the staging workup for each patient. Bone marrow biopsies were performed in 19 patients. All patients initially received cisplatin-based chemotherapy and concomitant whole-brain radiation therapy consisting of 3,600-4,800 cGy. Subsequently, 22 patients also received thoracic radiation therapy (17 patients as part of the protocol treatment and five patients at the time of disease progression). Thirteen patients had a complete response, 11 had a partial response, three had regression, and three had stable disease. Median survival of the entire group was 14 months (range, 1.4-70.7 months). Twenty-four patients eventually had progression of disease, with a median time to progression of 10 months (range, 2.3-48.5 months). Only one patient had disease progression in the brain (12.6 months after diagnosis). Twenty-two patients eventually died of the disease. The results of our study suggest that the therapeutic outcome in SCLC with the brain as the single site of metastases at initial diagnosis is similar to that of limited-stage SCLC.
TL;DR: It is concluded that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent.
Abstract: In literature data, an uncertainty exists whether occurrence of bilateral breast cancer decreases the survival probability of affected patients. Therefore, we analyzed the medical records of 498 postoperatively irradiated (1977-1982) female breast cancer patients (T1-4,N0-3,M0). In the follow-up time, in 36 patients a bilateral breast carcinoma treated by surgery with or without radiotherapy was found. The 10-year overall survival rates were 54% in patients who had unilateral disease, compared with 56% in bilateral carcinoma patients, respectively. The incidence of metastasis did not differ between both groups: 24.2% versus 38.8%. Eleven percent of unilateral cancers recurred; in the other group, local failure of the first and second tumor was observed in 19.4% and 11.1%, respectively. We conclude that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent. The therapeutic strategy in bilateral carcinoma should resemble the treatment procedure in unilaterally affected patients.
TL;DR: Determination of the presence of a K-ras mutation may predict survival in patients with progressive colon cancer after treatment with 5-fluorouracil who receive CPT-11.
Abstract: Objective: To determine the prognostic role of a K-ras mutation in tumor tissue of patients with refractory colon cancer who received irinotecan hydrochloride (CPT-11). Methods: DNA was extracted from paraffin-stored tumor tissue of 35 patients with progressive colon cancer failing treatment with 5-fluorouracil who subsequently received CPT-11 (100 mg/m2 i.v. per week × 4 weeks with 2 weeks off per course). The first exon of the K-ras gene was amplified by polymerase chain reaction by using K-ras-specific primers followed by mutant enrichment sequencing. Survival differences of patients with a K-ras mutation were compared with those of patients with a normal K-ras status. Results: A total of 21 patients had a normal K-ras sequence and 14 patients had a K-ras mutation [GAT, n = 7; TGT, n = 3; and GCT, AGT, GTT, GAC (codon 13), n = 1 each]. Median survival of patients with a normal ras sequence from time of treatment with CPT-11 was 332 days compared with 169 days for patients with a K-ras mutation (p = 0.0036). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. Conclusion: Determination of the presence of a K-ras mutation may predict survival in patients with progressive colon cancer after treatment with 5-fluorouracil who receive CPT-11.
TL;DR: This study highlights the need to select patients with a good prognosis for atypical oracles for initial treatment with chemotherapy or radiation on theignant gliomas when the prognosis is poor.
Abstract: Malignant gliomas are primary CNS tumors with a poor prognosis which has not improved recently.
TL;DR: This retrospective study evaluates the efficacy of megestrol acetate in patients with hormone refractory metastatic metastatic adenocarcinoma of the prostate and shows little activity, and cannot recommend megestro acetate as an effective second-line therapy.
Abstract: This retrospective study evaluates the efficacy of megestrol acetate in patients with hormone refractory metastatic adenocarcinoma of the prostate. Data are presented from 14 patients with advanced prostatic adenocarcinoma who were treated with 160-320 mg of megestrol acetate daily. Each patient was either asymptomatic or had minimal cancer-related symptoms. Disease response was monitored by prostate-specific antigen levels. The response rate was 14%, with two patients having a partial response. No complete responses were observed. The median time to disease progression was 2 months. Our findings when considered together with results from previously published data demonstrate little activity of megestrol acetate in patients with hormone refractory prostate cancer. Therefore, we cannot recommend megestrol acetate as an effective second-line therapy.
TL;DR: In cancer patients with elevated effusion levels of specific tumor markers, the effusions could be considered of a malignant nature even without cytologically demonstrable tumor cells.
Abstract: To assess the possibility of increasing the detection rates of cytological examination in malignant effusions by the selection of specific tumor markers for a given type of tumor, we measured CEA, CA 19.9, CA 15.3, MCA, PSA, and AFP in malignant effusions from 89 patients with the following primary malignancies: colon, stomach, breast, liver, prostate, lung, and kidney. Cytological examination was positive in only 35 of 89 patients (40%), while the tumor markers were positive in 72 of 89 cases (80%). However, apart from small cell lung and kidney cancers, where the lack of a specific tumor marker resulted in no advantage, in the other types of tumors, the specific marker for each tumor identified correctly malignant effusions in 72 of 74 cases (97%). In fact, CEA was positive in 11 of 11 effusions induced by colorectal cancer; CA 19.9 in 28 of 30 gastric cancer effusions, while MCA and CA 15.3 were positive in breast cancer effusions (16/22 and 20/22). Finally, elevated AFP and PSA indicated hepatocellular and prostate cancer, respectively. In conclusion, in cancer patients with elevated effusion levels of specific tumor markers, the effusions could be considered of a malignant nature even without cytologically demonstrable tumor cells.
TL;DR: The combination of continuous infusion of carboplatin and radiotherapy at the aforementioned doses in patients with locally advanced cervical carcinoma resulted in a relatively low frequency of significant acute and late complications.
Abstract: OBJECTIVE A prospective, single-arm phase-I/II trial performed to assess the efficacy and toxicity of the concomitant use continuous infusion of low-dose carboplatin and pelvic conventional radiotherapy in patients with locally advanced squamous cell carcinoma of the cervix. MATERIALS AND METHODS Between January and July 1994, a total of 12 patients consecutively diagnosed to have squamous cell carcinoma of the cervix uteri stages IIB-IIIB UICC-TNM (five patients, IIB; and seven patients, IIIB) entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pretreatment staging procedures. Radiation was delivered with 10-MeV photon beams with the shrinking-field technique. The patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 60 Gy in 6 weeks to the primary tumor and 46 Gy in 4 weeks to the whole pelvis. Irradiation was performed using four fixed orthogonal fields. One intracavitary insertion, 8 Gy to point A (dose rate, 1.1 Gy/h), was performed immediately after external pelvic irradiation. Carboplatin (12 mg/m2/day) was also administered in a continuous infusion, starting 1 day before the first fraction of radiotherapy. The platinum in plasma and urine, as well as the platinum concentration in the cytosols of lymphocytes and tumor, was measured weekly. RESULTS A complete response was seen in nine (75%) of the 12 patients. Of the nine patients who achieved a complete remission, only one had subsequent failure in the pelvis. The total pelvic failure rate was 33.3% (four of 12 patients). With a median follow-up time of 20 months, the actuarial survival rate at 24 months was 64.8%. All patients completed the treatment without major protocol violations. Grade-2 leukopenia (in nine patients) and grade-1 nausea and vomiting (in five) were the most common acute toxicities. There was one grade-3 hematologic toxicity. Grade-3 late complications were observed in 16.6% of cases (two of 12 patients). On days 28 and 42 of the treatment, the mean total platinum plasma concentrations were 491 micrograms/L (SD = 129) and 672 micrograms/L (SD = 160), and the ultrafilterable fraction was 8-10%. At the same time points, the concentration in lymphocytes was constant at 21 picograms (pg) platinum/lymphocyte. The levels of platinum concentration measured on days 14 and 28 in the cytosols of tumor cells were 0.3 microgram/g (SD = 0.1) and 0.93 microgram/g (SD = 0.2). CONCLUSION The combination of continuous infusion of carboplatin and radiotherapy at the aforementioned doses in patients with locally advanced cervical carcinoma resulted in a relatively low frequency of significant acute and late complications. Platinum in normal tissue (picograms per lymphocyte) was stable from week 1 of treatment, whereas the platinum steady state in plasma and in tumor cells was not reached in 6 weeks and was below that required in vitro to produce radiopotentiation. Further studies to determine the optimal dose of carboplatin and irradiation are needed prior to the initiation of phase-III studies.
TL;DR: Topotecan is a well-tolerated new agent with similar single-agent activity to that of cisplatin, 5-fluorouracil, and methotrexate in advanced head and neck cancer and is suitable for use with other chemotherapeutic drugs and with concurrent radiation therapy.
Abstract: This study evaluated the efficacy and safety of topotecan, a topoisomerase I inhibitor, in patients with advanced squamous cell cancer of the head and neck. Topotecan was administered intravenously (over 30 min) daily for 5 days every 3 weeks at a starting dose of 1.5 mg/m2/day. Eligibility required no prior chemotherapy, measurable disease, and performance status of < or = 2. Quality of life (QOL) assessment was performed at specified time points using the Spitzer QOL index and the symptom distress scale. Of 26 patients entered into the study, 23 and 22 patients were assessable for toxicity and response, respectively. One complete and two partial responses were observed, with response durations of 9, 4, and 1.5 months, respectively. Six patients had stable disease, including one patient with a 45% tumor shrinkage. The median survival for all patients entered was 4 months. Neutropenia was the major dose-limiting side effect, with grade 4 toxicity observed in 42% of all cycles of treatment. Grade 3 anemia occurred in 16% of all cycles, and nine patients required blood transfusions. Nonhematologic toxicities were infrequent and mild to moderate. QOL assessment revealed no significant change of total scores between each assessment point. Topotecan is a well-tolerated new agent with similar single-agent activity to that of cisplatin, 5-fluorouracil, and methotrexate in advanced head and neck cancer. Further investigation of this agent with other chemotherapeutic drugs and with concurrent radiation therapy is appropriate.
TL;DR: HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatins concurrent with standard RT.
Abstract: A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.
TL;DR: The effects of the addition of escalating doses of tumor necrosis factor to two fixed doses and schedules of a combination of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) to determine the maximum tolerated dose and its feasibility as an outpatient regimen were evaluated.
Abstract: We evaluated the effects of the addition of escalating doses of tumor necrosis factor (TNF) to two fixed doses and schedules of a combination of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) to determine the maximum tolerated dose of this three-cytokine combination and its feasibility as an outpatient regimen. Eighteen patients with metastatic cancer were enrolled. Each course consisted of 3 consecutive weeks of treatment with IFN-alpha 9 x 10(6) IU/m2/day intramuscularly (i.m.) or subcutaneously (s.c.) days 1, 3, and 5 each week for 3 weeks plus IL-2 continuous infusion 1 x 10(6) IU/m2/day (group A) or 3 x 10(6) IU/m2/day (group B) days 1-5 each week for 3 weeks. TNF was administered only during the first week of each course intravenously (i.v.) for 2 h on days 1-5. The dose of TNF was escalated (40, 80, 120 micrograms/m2) in cohorts of 3 patients. The most common side effects were fever, chills, and fatigue in all patients. Grade 3-4 toxicity included anemia (3 patients), thrombocytopenia (1 patients), arrhythmia (2 patients), pulmonary edema (3 patients),- and weight loss (1 patient). Five patients withdrew from study due to toxicity. The combination of the three cytokines is feasible as an outpatient regimen in one of the following combinations: (a) TNF 80 micrograms/m2/day as 2-h infusion on days 1-5 + IL-2 1 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks, or (b) TNF 40 micrograms/m2/day as a 2-h infusion on days 1-5 + IL-2 3 x 10(6) IU/m2/day continuous infusion on days 1-5 for 3 weeks + IFN-alpha 9 x 10(6) IU/m2/day s.c. or i.m. on days 1, 3, and 5 for 3 weeks.