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PubMed2004

Carcinoma of unknown primary site: sequential treatment with paclitaxel/carboplatin/etoposide and gemcitabine/irinotecan: a Minnie Pearl Cancer Research Network phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of the sequential administration of paclitaxel (Taxol; Bristol-Myers Squibb; Princeton, NJ), carboplatin (Paraplatin; Bristol-Myers Squibb), and oral etoposide (VePesid; Bristol-Myers Squibb) followed by gemcitabine (Gemzar; Eli Lilly; Indianapolis, IN) and irinotecan (Campostar; Pfizer Pharmaceuticals; New York, NY) in the first-line treatment of patients with carcinoma of unknown primary site. PATIENTS AND METHODS: One hundred thirty-two patients were treated with sequential combination chemotherapy for a maximum of six cycles. All patients had relatively poor prognostic features. Fifty-nine patients had well-differentiated adenocarcinoma, 73 patients had poorly differentiated carcinoma, and 121 patients had performance status scores of 0 or 1. RESULTS: Thirty-three (30%) of 111 assessable patients (95% confidence interval 27%-33%) had objective responses to treatment (26 partial responses, seven complete responses). The combination of gemcitabine and irinotecan was associated with significantly less toxicity than the triple-drug regimen and improved the responses in several patients (10%). The response rates were similar in the two major histologic tumor types, but were lower for patients with liver-dominant tumors (13%) and higher for patients with lymph-node-dominant tumors (50%). The median progression-free survival time, median survival time, and actuarial survival rates at 1 and 2 years were 5.7 months, 9.1 months, 35%, and 16%, respectively. CONCLUSIONS: Sequential combination chemotherapy with paclitaxel/carboplatin/oral etoposide and gemcitabine/irinotecan is an active treatment for patients with carcinoma of unknown primary site, but overall toxicities are greater than those seen with other combinations of new drugs and survival appears similar to that observed in 264 other patients treated in our four previous phase II trials. A better understanding of the biology of these heterogeneous tumors will likely lead to improved therapy for these patients.

Adult↗
PubMed1992

Intracavitary administration of interleukin-2 as palliative therapy for neoplastic effusions.

Cytokines have recently appeared to be effective in the palliative therapy of neoplastic effusions. The present study was carried out to evaluate the efficacy and the tolerability of an intracavitary injection of IL-2 in patients with neoplastic effusion due to solid tumors. The study included 14 patients with cytologically positive effusion (pleura, 11; peritoneum, 2; pericardium, 1). Tumor histotypes were: mesothelioma, 5; non-small cell lung cancer, 3; breast cancer, 2; ovarian cancer, 2; cervix carcinoma, 1; unknown primary tumor, 1. The efficacy was evaluated according to the criteria of Paladine et al. (Cancer 38: 1903, 1976). An objective response was achieved in 10/14 (71%) patients (4 CR, 6 PR), with a median duration of 4 months (range, 2-8). No important toxicity was seen. This preliminary study showed that low dose IL-2 given intracavitarily is an effective and well-tolerated therapy in patients with neoplastic effusions.

Adult↗
PubMed2006

Genomic sweeping for hypermethylated genes.

MOTIVATION: Genes silenced by the aberrent methylation of nearby CpG islands can contribute to the onset or progression of cancer and represent potential biomarkers for diagnosis and prognosis. Relatively few have thus far been validated as hypermethylated in cancer among over 14,000 candidates with promoter region CpG islands. A descriptive set of genes known to be unmethylated in cancer does not exist. This lack of a negative set and a large number of candidates necessitated the development of a new approach to identify novel genes hypermethylated in cancer. RESULTS: We developed a general method, cluster_boost, that in an imbalanced data setting predicts new minority class members given limited known samples and a large set of unlabeled samples. Synthetic datasets modeled after the hypermethylated genes data show that cluster_boost can successfully identify minority samples within unlabeled data. Using genome sequence features, cluster_boost predicted candidate hypermethylated genes among 14,000 genes of unknown status. In primary ovarian cancers, we determined the methylation status for 15 genes with different levels of support for being hypermethlyated. Results indicate cluster_boost can accurately identify novel genes hypermethylated in cancer. AVAILABILITY: Software and datasets are freely available at http://labs.genome.duke.edu/FureyLab/cluster_boost.php. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗
PubMed2006

Microarrays in gastrointestinal cancer: is personalized prediction of response to chemotherapy at hand?

PURPOSE OF REVIEW: Molecular profiling has proven to be an invaluable tool in cancer research. Although only in its infancy, microarray technology and gene arrays have led to substantial advances in tumor identification, staging and prediction of response. This review outlines some of the more recent advances in the use of microarrays as a novel means to advance the standard of care for patients with gastrointestinal cancers. RECENT FINDINGS: Recent investigations have shown that gene expression profiles can be used to identify, stage, and guide therapeutic intervention in many gastrointestinal cancers. In cases of unknown primary disease, genetic fingerprints can be used to define the origin of the tumor in the majority of cases. Similarly, gene expression has been shown to allow for more accurate staging of patients with a variety of tumor types. Perhaps most exciting is early data that support the potential for microarray to guide therapeutic intervention by providing specific gene fingerprints which correlate with sensitivity to specific chemotherapy, biologic therapy, or other cancer treatments. SUMMARY: Gene microarrays have become a powerful resource in cancer investigations. Individualized cancer care based on specific gene profiles is on the horizon for patients with gastrointestinal cancers.

Antineoplastic Agents↗
PubMed2006

Merkel cell carcinoma and multiple primary cancers.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for which causative factors remain largely unknown. The site-specific risks of multiple primary cancers associated with MCC, which may provide insight into etiologic influences, have not been quantified in large population-based studies. We estimated the long-term risk of subsequent primary tumors after a first primary MCC (1,306 patients) and the risk of second primary MCC following other first primary cancers (2,048,739 patients) within 11 population-based cancer registries which report to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1986-2002). Patients with first primary MCC were at significantly increased risk of developing a subsequent cancer [standardized incidence ratio (SIR), 1.22; 95% confidence intervals (95% CI), 1.01-1.45; observed (O = 122)], with significant excesses restricted to the first year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly elevated site-specific risks were observed for cancers of salivary gland (SIR, 11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95% CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were seen for chronic lymphocytic leukemia, and cancers of the small intestine and brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of MCC as a second primary malignancy was observed among patients with all other first primary cancers taken together. In particular, significant 3- to 7-fold excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4), chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR, 3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play a role, increased reciprocal risks suggest that MCC may share etiologic influences with other malignancies. Heightened awareness of the associations of lymphohematopoietic malignancies with MCC may facilitate early clinical recognition.

Aged↗
PubMed1994

The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.

The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

Adenocarcinoma↗
PubMed2006

Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.

PURPOSE: To determine the recommended starting doses and pharmacokinetics of irinotecan in cancer patients with impaired liver function treated on a weekly schedule. EXPERIMENTAL DESIGN: Patients with solid tumors who had impaired liver function were enrolled into four groups based on baseline serum total bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT): Group 1 (n = 19): total bilirubin 1.5 to 3.0 x institutional upper limit of normal (IULN) and ALT/AST <or=5.0 x IULN; Group 2 (n = 7): total bilirubin 3.1 to 5.0 x IULN and ALT/AST <or=5.0 x IULN; Group 3 (n = 6): total bilirubin <or=1.5 x IULN and ALT/AST 5.1 to 20.0 x IULN; Group 4 (n = 10): total bilirubin 1.5 to 3.0 x IULN and ALT/AST 5.1 to 20.0 x IULN. Irinotecan was given as a 90-minute i.v. infusion weekly for the first 4 weeks in each 6-week cycle at starting doses which escalated from 40 to as much as 75 mg/m(2). After the first treatment, doses were adjusted based on individual patient toxicities. Starting doses for patients with hepatic dysfunction were derived from the maximum tolerated doses noted in the four hepatic dysfunction groups. RESULTS: Forty-two patients were treated. Among the most frequent adverse events were neutropenia (41%, grades 3/4), diarrhea (15%, grades 3/4), nausea (10%, grade 3), and vomiting (5%, grades 3/4). Two patients died from drug-induced neutropenic sepsis. Two patients had objective tumor responses (complete response, liver metastases from unknown primary; partial response, colon cancer). Hepatic dysfunction reduced irinotecan clearance while increasing relative exposure to the active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). SN-38 exposures in patients receiving doses of 40 to 75 mg/m(2) were comparable to exposures in patients with normal liver function treated with a starting dose of 125 mg/m(2). CONCLUSIONS: Irinotecan starting doses that seem to be safe for hepatically impaired patients treated with the weekly schedule are 60, 50, 60, and 40 mg/m(2) for groups 1 to 4, respectively. At these starting doses, exposure to SN-38 and the adverse event profile are similar to that observed in patients with normal liver function and antitumor activity can be observed.

Adult↗
PubMed2001

Radiotherapy of the neuroaxis for palliative treatment of leptomeningeal carcinomatosis.

BACKGROUND: Leptomeningeal carcinomatosis occurs in about 5% of solid tumors and may seriously compromise quality of life. Aim of the present study was to evaluate the feasibility of craniospinal irradiation with and without intrathecal chemotherapy and its efficacy with regard to symptom palliation and survival. PATIENTS AND METHODS: 16 patients (mean age 46 years; nine breast cancers, five lung cancers, one renal cell cancer, one tumor of unknown primary site) with leptomeningeal carcinomatosis occurring after a median interval from primary tumor diagnosis of 5 months (0-300 months) received craniospinal irradiation between October 1995 and May 2000. The median total dose was 36 Gy (à 1.6-2.0 Gy). Ten patients were additionally treated with intrathecal methotrexate (15 mg per cycle, 2-8 cycles). RESULTS: Median survival was 12 weeks, 8 weeks after radiotherapy alone, 16 weeks after combined modality treatment. 14 patients died from disease. Eleven patients (68%) experienced regression of their neurological symptoms during or soon after completion of radiotherapy. Seven patients regained their ability to walk, six had pain reduction, three regression of bladder and bowel incontinence. In three patients symptom progression and in two patients no change occurred. Side effects were: myelosuppression (CTC) Grade I: n = 2, Grade II: n = 4, Grade III: n = 4 patients and Grade IV: n = 1. Nine patients had dysphagia, seven mucositis, three suffered from nausea. No late toxicity was observed. CONCLUSION: Craniospinal radiotherapy is feasible and effective for palliative treatment of leptomeningeal carcinomatosis. As far as the small patient number permits any definite conclusions, combined modality treatment seems superior to irradiation alone.

Adult↗
PubMed1997

Phase I study of treatment with oral 13-cis-retinoic acid, subcutaneous interferon alfa-2a, cisplatin, and 24-hour infusion 5-fluorouracil/leucovorin.

UNLABELLED: A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used for SCCAs. PURPOSE: To determine the maximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase II regimen for testing in cervical cancer and other appropriate tumor types. METHODS: Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA was given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily. RESULTS: A total of 31 patients were treated. The IFN dose was reduced to 3 MU three times weekly because of patient intolerance. Cytopenias prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three times weekly IFN and twice daily cis-RA was tolerable. Four partial responses were observed, in patients with adrenal cancer, bladder cancer, gastric cancer, and adenocarcinoma of unknown primary. CONCLUSIONS: The recommended phase II regimen is cisplatin 100 mg/m2 every 3 weeks, IFN 3 MU three times weekly, and cis-RA 1 mg/kg daily. This appears to be more toxic than single-agent cisplatin, but the preliminary activity observed warrants further testing.

Administration, Oral↗
PubMed2004

Bone metastases revealing primary tumors. Comparison of two series separated by 30 years.

OBJECTIVE: To compare two series of patients admitted to a rheumatology department for bone metastases 30 years apart and to obtain a pragmatic estimation of the percentage of bone metastases revealing cancer. METHODS: The recent series was composed of 132 patients seen between 1989 and 1996 and the earlier series of 50 patients admitted between 1958 and 1967. All patients were admitted to the same rheumatology department for bone metastases from a diagnosed or undiagnosed primary. Both series were studied retrospectively. The rate of occurrence of each cancer diagnosis was determined in the patients with and without known primaries. RESULTS: Among the patients with metastatic disease as the first manifestation of cancer, the percentage with lung cancer increased from the early to the recent series, particularly among women, whereas the percentages with prostate and breast cancer decreased. The primary remained unknown in 27% and 38% of patients in the early and recent series, respectively. CONCLUSION: Despite the introduction of new investigations, our ability to identify primaries responsible for bone metastases does not seem to have improved. However, our data should be interpreted with caution since recruitment probably differed between the two series.

Adult↗
PubMed1989

Combination chemo-radiation therapy for jaundice due to focal malignant obstruction of the major bile ducts.

Twenty patients with focal malignant obstruction of the major bile ducts (6 cholangiocarcinoma, 8 colorectal, 3 hepatoma, 2 unknown primary, and 1 gastric cancer) were treated on a protocol examining the toxicity and efficacy in relieving jaundice of external beam radiation therapy (4500 cGy in 300 cGy fractions) combined with continuous hepatic arterial (15 patients) or peripheral venous (5 patients) fluorouracil infusion. Toxicity of this regimen consisted of anorexia with mild nausea and vomiting in 55% of patients and gastric ulceration (responsive to medical management) in 15% of patients. One patient exhibited transient grade 2 hepatic toxicity and one had asymptomatic grade 4 leukopenia. Of 14 patients treated without prior biliary drainage, 8 exhibited a decrease in bilirubin levels from a mean of 14.5 mg/dl to 1.5 mg/dl. Four of six patients with biliary drainage catheters at the start of treatment were able to have them removed without reobstruction. For the 8 responding patients among those who did not have cholangiocarcinomas, the median response duration was 5 months with a median survival from treatment of 6.5 months. For the 4 responding patients with cholangiocarcinoma, the median response duration was 16 months with a median survival from treatment of 20 months. All responders did not have a return of jaundice due to reobstruction of the major ducts (until death or to the present). All responders who have died did so due to tumor progression outside of the treated field except for one who died of unrelated causes. The mean number of proven or presumed episodes of cholangitis per patient was virtually identical in those without (1.8) and those with stents/tubes (1.4, p = 0.561). This regionally focused combined modality cytotoxic therapy was able to relieve obstruction in the majority of patients without excess morbidity (including a lack of any detectable increase in sepsis). Thus, it appears feasible to consider randomized studies of this cytotoxic approach versus standard mechanical drainage procedures to define the relative risks and benefits of each.

Adult↗
PubMed2005

Identification of occupational cancer risks in British Columbia: a population-based case-control study of 1129 cases of bladder cancer.

OBJECTIVE: We collected information on lifetime occupational histories, smoking, and alcohol consumption from 15,463 incident cancer cases. Occupational risk factors for bladder cancer are presented in this report. METHOD: A matched case-control design was used. All cases were diagnosed with bladder cancers, with controls being internal controls consisting of all other cancer sites, excluding lung and unknown primary. Data were analyzed using conditional logistic regression for matched sets data and the likelihood ratio test. RESULTS: Excess bladder cancer risks was observed in a number of occupation and industries, particularly those involving exposure to metals, including aluminum, paint and solvents, polycyclic aromatic hydrocarbons, diesel engine emissions, and textiles. CONCLUSIONS: The results of our study are in line with those from the literature and further suggest that exposure to silica and to electromagnetic fields may carry an increased risk of bladder cancer.

Adult↗
PubMed1998

Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen.

PURPOSE: Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder. PATIENTS AND METHODS: Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure. RESULTS: Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia. CONCLUSION: A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.

Adult↗
PubMedDate not supplied

One-hour paclitaxel infusions: review of safety and efficacy.

PURPOSE: Paclitaxel has emerged as one of the most active anticancer agents in clinical oncology. Hypersensitivity reactions encountered in the clinical development of this drug prompted the implementation of premedication regimens and prolonged infusions, later amended to a 3-hour infusion schedule. Now that paclitaxel is frequently used in outpatient therapy, optimum efficiency in delivery is an issue. A 1-hour drug infusion is more efficient for both the patient and the clinic staff and can help reduce administration costs. This article reviews the current experience with 1-hour paclitaxel infusions. METHODS: Published studies using 1-hour paclitaxel infusions, including weekly studies, trials of combination chemotherapy, and combined-modality studies, were reviewed. Studies were evaluated for both efficacy and toxicity. RESULTS AND CONCLUSIONS: Paclitaxel administered by 1-hour infusion as part of weekly or every-3-week treatment regimens is active in a variety of tumors, including breast, ovarian, and lung cancer and carcinoma of unknown primary site. Leukopenia, the most common serious toxicity, is usually manageable without hematopoietic growth factor support. The frequency of neurotoxicity appears comparable for 1-hour and 3-hour regimens, and there is no increased risk of hypersensitivity reactions. Infusion duration has been suggested to be an important predictor of response in some tumor types. Evaluation of this issue using a 1-hour paclitaxel infusion as reference is reasonable. One-hour infusions of paclitaxel should simplify outpatient administration, reduce administration costs, and reduce clinic time for patients. Practical information regarding administration of paclitaxel by 1-hour infusion is provided.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Activation of p53 protein in normal and in tumor cells by a novel anticancer agent CHS 828.

CHS 828, a novel cyanoguanidine, represents a new class of drugs for cancer therapy, with an unknown primary mechanism of action. It is generally known that anticancer drugs induce p53 response thereby triggering cell cycle arrest or apoptosis. We investigated the effect of CHS 828 on p53 response in normal and tumor cells and compared this effect with that exerted by conventional anticancer drugs. After 24 h of treatment with CHS 828, we observed a dose-dependent up-regulation of wild type (WT) p53 protein in human breast carcinoma MCF-7 cells as well as in normal human and mouse fibroblasts. The highest p53 increase was observed at 300 nM to 1 microM CHS 828. CHS 828 induced phosphorylation of p53 protein at Ser-15 in normal cells. However, the drug failed to induce p53 protein in mouse cells in which the poly(ADP-ribose)-1 gene (PARP-1) was disrupted even at a 30-fold higher dose and after prolonged treatment. Combined treatment of PARP-1 -/- cells by multidrug resistance modulators did not alter p53 expression. CHS 828 inhibited cell proliferation and DNA replication in the tested cells. Interestingly, DNA synthesis as well as proliferation of PARP-1 deficient cells was inhibited by drug concentrations that were approximately 3-fold lower than their conventional counterparts. Treatment of cells with CHS 828 for 48 h did not induce apoptosis.

Animals↗
PubMed1993

Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion.

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.

Adult↗
PubMed1999

[Adenocarcinoma of unknown primary site with thoracic localization and HIV: four case reports].

INTRODUCTION: Non AIDS-defining cancer would have increased in HIV-patients as suggested by numerous studies. Four cases of adenocarcinoma of unknown primary site with thoracic localization that occurred in HIV-infected patients are described. EXEGESIS: To date, there have been no published data about carcinomas of unknown primary site relating to HIV-infected patients; however, immunodepression could promote them. Carcinomas of unknown primary site account for 0.5 to 10% of all cancer in general population. Primary carcinoma is identified in approximately one third of the cases and often corresponds to lung cancer in case of sus-diaphragmatic metastasis, particularly in case of pleural metastasis. Lung cancer in HIV-infected patients affects mostly young men who smoke and are often intravenous drug addicts. Adenocarcinoma is the most common histological type of cancer. CONCLUSION: Further studies of lung cancer in HIV-infected patients will help evaluate their frequency. In case of increasing frequency, lung cancer should then be included in AIDS-defining cancers.

Adenocarcinoma↗
PubMed2002

CT features of intracranial metastases of unknown primaries.

Intracranial metastases of central nervous system are relatively common in patients with systemic cancer. Computed tomography (CT) scans of 60 patients of intracranial metastatic disease of unknown primaries, at the time of surgery, were retrospectively analyzed. These patients primarily presented with neurological dysfunction. They were operated upon for various reasons and histopathological diagnosis was obtained. There were 39 male and 21 female patients, with age range of 18 to 74 years. The common clinical symptoms were raised intracranial pressure without lateralization, acute onset hemiplegia and seizures. Multiple cranial nerve palsies were observed in 4 patients. Histopathologically the intracranial lesions consisted of metastatic adenocarcinoma (32 cases) or metastatic squamous cell carcinoma (28 cases). Among cases of adenocarcinoma, CT revealed solitary lesions in 17 and multiple lesions in 13 cases. Two had extraaxial deposition in the region of petrous apex. Out of squamous cell carcinomas, 17 lesions were solitary, while 10 were multiple and one had extraaxial deposition in the region of petrous apex. This study is unique as it consisted of CT features of intracranial metastases of unknown primary malignant disease elsewhere in the body.

Adenocarcinoma↗