J Clin Oncol 2006 May 22; (Read article online)

Cachin F, Prince HM, Hogg A, Ware RE, Hicks RJ

PURPOSE: This study examines the use of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of the therapeutic response for patients treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation for metastatic breast cancer (MBC) focusing on prognostic stratification. PATIENTS AND METHODS: Forty-seven patients with MBC were treated with a maximum of three cycles of HDC. Therapeutic response was assessed with conventional imaging (CImg; including a computed tomography in all cases and ultrasound, mammography, and bone scanning as clinically indicated) and by FDG-PET study performed after the last cycle of HDC. Parameters analyzed for predicting survival were FDG-PET and CImg results, pattern of disease, prior treatment, and HDC regimen. RESULTS: Complete responses were observed in 16 patients (37%) with CImg and 34 patients (72%) with FDG-PET. The FDG-PET result was the most powerful and independent predictor of survival; patients with a negative post-treatment FDG-PET had a longer median survival than patients with a positive FDG-PET (24 months v 10 months; P < .001). By multivariate analysis the relative risk (RR) of death was higher in patients with FDG-PET-positive disease (RR, 5.3), prior anthracycline treatment (RR, 3.3), or with visceral metastasis (RR, 2.4). CONCLUSION: A single FDG-PET study performed after completion of HDC for MBC can powerfully stratify for survival. This may have implications for how we should assess outcome after conventional-dose therapy for MBC and warrants additional study.

Semin Oncol 2006 Apr; 33(2 Suppl 6): 3-11 (Read article online)

Ozols RF

Current systemic therapy for ovarian cancer consists of a combination of carboplatin and paclitaxel. While the majority of patients achieve clinical complete remission after six cycles of chemotherapy, the relapse rate stands at over 50%. Median survival time for patients after recurrence is approximately 2 years. New treatment approaches for patients with advanced ovarian cancer include consolidation and maintenance therapy, intraperitoneal administration of cytotoxic agents, new combination chemotherapy regimens, the development of new cytotoxic agents, and molecular-targeted therapies. These agents will be evaluated either singularly or with chemotherapy. Currently, the Gynecologic Oncology Group is evaluating a combination of bevacizumab together with paclitaxel and carboplatin in previously untreated patients with advanced ovarian cancer. This trial is based on phase II data that suggest that bevacizumab as a single agent has significant activity in patients with recurrent ovarian cancer. In addition, the Gynecologic Oncology Group will be conducting phase II trials of different combinations of intraperitoneal chemotherapy in an effort to decrease toxicity associated with current intraperitoneal regimens that have shown an improvement in survival in patients with small-volume stage III disease. The Gynecologic Oncology Group will also be conducting a trial of maintenance therapy in patients who enter clinical complete remission with paclitaxel plus carboplatin, comparing observation with monthly paclitaxel or monthly paclitaxel poliglumex. Novel new cytotoxic and biologic agents are also being evaluated as single agents in phase II trials in patients with recurrent ovarian cancer.

Semin Oncol 2006 Apr; 33(2 Suppl 6): 33-8 (Read article online)

Markman M

Despite substantial documented progress in the chemotherapeutic management of women with gynecologic malignancies, a number of highly clinically relevant issues remain unresolved. In ovarian cancer, questions asked by practicing oncologists, patients, and their families include the role of maintenance chemotherapy in routine management of the disease, determining which patients with early stage disease do not require cytotoxic therapy, defining the most appropriate management paradigm for both recurrent and resistant cancer, determining which taxane to combine with carboplatin in the first-line regimen, and developing an optimal intraperitoneal primary chemotherapy regimen for small-volume residual advanced disease. In endometrial cancer, important issues include defining first-line chemotherapy for metastatic or recurrent disease and mixed mesodermal endometrial cancer, and determining whether there is a role for adjuvant cytotoxic chemotherapy in the setting of high-risk early stage cancer. Finally, in cervical cancer, there is a critical need to determine the most appropriate treatment strategy for metastatic cancer, as well as to find an effective second-line treatment option for platinum-resistant disease. It is reasonable to anticipate that future clinical trials will answer these and other unresolved issues, just as past well-designed studies have resulted in major improvements in both the survival and quality of life of women with this group of malignancies.

Scand J Gastroenterol 2006 Jun; 41(6): 673-81 (Read article online)

Hollender A, Bjøro T, Otto Karlsen K, Kvaloy SO, Nome O, Holte H

Objective. To determine the nutritional status in patients treated for gastric non-Hodgkin's lymphoma (NHL).Material and methods. Patients treated during the period 1990-99 according to a protocol including primary gastric surgery for eligible patients were registered prospectively in successive patients. Those with aggressive lymphomas in stage IE-IIE underwent gastric surgery followed by CHOP-like chemotherapy. Patients with indolent lymphomas and localized disease did not receive any further treatment if the operation was considered radical; otherwise, they received local radiotherapy after surgery. Patients with advanced disease underwent gastric surgery only if there was a considerable risk of bleeding or perforation. Patients below the age of 80 years and in complete remission were offered a cross-sectional examination a median of 102 months later, including clinical examination with estimation of body mass index, upper endoscopy and blood tests (haemoglobin, ferritin, serum-Fe, total iron-binding capacity (TIBC), vitamin B(12), homocysteine, vitamin D status, parathyroid hormone (PTH), albumin and electrolytes).Results. Forty patients were identified, of whom 33 met for follow-up examination. Seventeen patients had a partial gastrectomy (PG), 9 a total gastrectomy (TG) and 7 patients were not operated on. The patients in the TG group had significant weight loss. Furthermore, the patients in the TG group had a lower storage iron content (s-ferritin and s-iron saturation), lower s-vitamin D, higher s-PTH and homocysteine than the other groups.Conclusions. If surgery is necessary for gastric lymphomas, a PG should be performed when possible. The patients should receive dietary advice and be followed-up at least yearly for nutritional deficiencies. Regular intake of vitamin D and -B(12), calcium, folate and iron should be considered.

J Clin Oncol 2006 May 22; (Read article online)

Bourhis J, Rivera F, Mesia R, Awada A, Geoffrois L, Borel C, Humblet Y, Lopez-Pousa A, Hitt R, Villegas ME, Duck L, Rosine D, Amellal N, Schueler A, Harstrick A

PURPOSE: This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Treatment comprised cetuximab (initial dose 400 mg/m(2) with subsequent weekly doses of 250 mg/m(2)) in combination with 3-week cycles of either cisplatin (100 mg/m(2)) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m(2)/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity. RESULTS: Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics. CONCLUSION: The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m(2)/d in combination with cisplatin or carboplatin can be recommended for additional studies.

Semin Oncol 2006 Apr; 33(2 Suppl 6): 26-32 (Read article online)

Thigpen T

The combination of paclitaxel and carboplatin is now established as the standard first-line chemotherapy regimen for advanced ovarian cancer. Ways in which this standard therapy can be further improved are being investigated, and several approaches have been taken. One approach is to integrate a different cytotoxic agent into the standard combination. Gemcitabine is one such cytotoxic agent that is of particular interest because it has activity in disease resistant to treatment with paclitaxel plus carboplatin, and also has a different mechanism of action to that of the two agents in the standard combination. Gemcitabine plus cisplatin has shown activity in phase II trials and results are awaited from a phase III trial comparing paclitaxel plus carboplatin with gemcitabine plus carboplatin doublets. Using agents sequentially has been shown to be as effective as using them in combination; therefore, using a gemcitabine plus platinum doublet sequentially with paclitaxel plus carboplatin has also been studied. A phase III trial has closed and results are expected shortly. Triplet combinations have also been shown to be effective in early stage trials, although dose-limiting myelosuppression occurs with gemcitabine plus paclitaxel plus carboplatin. Two phase III trials of this triplet have finished and are awaiting data maturation. Lastly, a sequential triplet of gemcitabine plus paclitaxel plus carboplatin has been investigated, but high pulmonary toxicity led to the study being halted. The role of gemcitabine in first-line advanced ovarian cancer will become much clearer once the results from the various phase III trials are published.

Semin Oncol 2006 Apr; 33(2 Suppl 6): 17-25 (Read article online)

Pecorelli S, Pasinetti B, Tisi G, Odicino F

Ovarian cancer represents the leading cause of death from gynecologic neoplasms. The chance of response to secondary treatment is currently disappointing; few agents have shown notable activity in recurrent/progressive patients. Among these agents, gemcitabine represents one of the most interesting newer antineoplastic agents, showing significant activity, synergism with cisplatin, and a mild toxicity profile in both platinum-sensitive and platinum-resistant (and also taxane-pretreated) recurrent/progressive patients. Moreover, first-line combination chemotherapy including gemcitabine has shown promising response rates in phase I and II studies. The ongoing phase III, five-arm, randomized Gynecologic Oncology Group Protocol 182/International Collaborative Ovarian Neoplasm 5 study should clarify the clinical impact of the addition of a third drug to the standard paclitaxel plus carboplatin treatment regimen.

J Pain Symptom Manage 2006 May; 31(5): 457-464 (Read article online)

Llanes LR, Fassbender K, Baracos VE, Watanabe S

Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.

Lung Cancer 2006 May 20; (Read article online)

Scartozzi M, Franciosi V, Campanini N, Benedetti G, Barbieri F, Rossi G, Berardi R, Camisa R, Silva RR, Santinelli A, Ardizzoni A, Crinò L, Rindi G, Cascinu S

Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunoistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in >/=50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in >50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.

Gynecol Oncol 2006 May 19; (Read article online)

Vistad I, Fosså SD, Dahl AA

OBJECTIVES.: Increasing survival rates of cervical cancer (CC) patients and the trend towards more toxic multimodal therapy have led to focus on the quality of life (QOL) of cervical cancer survivors (CCSs). The aim of this critical review was to summarize and discuss the research findings of QOL in CCSs based on self-report measures in terms of physical, psychosocial, and sexual well-being. METHODS.: Electronic databases were used to identify studies published between 1966 and August 2005. A quality assessment using methodological and treatment-related criteria was performed to distinguish between studies with good and less good methodology. RESULTS.: Twenty-three studies were included, whereof eight had a good methodology. Eight studies used at least one questionnaire that had not been validated previously, and only one of the validated questionnaires had been tested in former studies of CCSs. The studies with good methodology focused primarily on sexual and social function after treatment, and less on physical and psychological well-being. The trend is that radiotherapy is more associated with reduced QOL dimensions than surgery or chemotherapy. In earlier stages of CC and following surgery alone, there seem to be minor differences between CCSs and control groups concerning various QOL domains. CONCLUSIONS.: Reviewed studies indicate that quality of life in cervical cancer survivors is reduced compared to the general female population following radiotherapy, but less so following surgery and earlier stages of cervical cancer. Shortcomings of both methodology and content of the studies reviewed preclude definite conclusions concerning QOL for the moment.

Semin Oncol 2006 Apr; 33(2 Suppl 6): 12-6 (Read article online)

Pfisterer J, Ledermann JA

The majority of patients with ovarian cancer will relapse despite state-of-the-art first-line surgery and chemotherapy. There are two subgroups of patients with recurrent ovarian cancer: those with platinum-resistant disease and those with platinum-sensitive disease. Re-treatment with single-agent platinum has long been considered standard therapy for patients with platinum-sensitive disease, and, based on its favorable therapeutic profile, carboplatin has become the treatment agent of choice. High response rates are seen with platinum agents used in combination with paclitaxel or gemcitabine. The International Collaborative Group for Ovarian Neoplasia (ICON) and the Arbeitsgemeinschaft für Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) recently conducted a trial (ICON4/AGO-OVAR-2.2) comparing platinum monotherapy with platinum plus paclitaxel combined. Results showed that overall survival and progression-free survival are improved by combination therapy. Similarly, a significant benefit in progression-free survival for carboplatin plus gemcitabine versus carboplatin monotherapy was seen in the Gynecologic Cancer InterGroup trial. The toxicity profiles and schedules of carboplatin plus paclitaxel and carboplatin plus gemcitabine are different, with the taxane combination having greater neurotoxicity and alopecia, less hematologic toxicity, and requiring longer drug infusions (although fewer days of treatment per cycle) than the gemcitabine combination. Based on the results of these two trials, combination chemotherapy should be considered the standard treatment of recurrent platinum-sensitive ovarian cancer. The choice of treatment needs to take into account the increase in side effects when using combination chemotherapy compared with carboplatin monotherapy, and the different toxicities of the two combination regimens.

Melanoma Res 2006 Jun; 16(3): 245-248 (Read article online)

Oʼneill PA, Butt M, Eswar CV, Gillis P, Marshall E

Uveal melanoma is relatively uncommon accounting for fewer than 5% of all melanoma cases. Localized tumours are curable by local therapy but a significant percentage of patients go on to have a relapse with metastatic disease. Uncertainty remains concerning the level of activity of dacarbazine in uveal melanoma as opposed to that in the cutaneous form. Recently, a possible role for treosulfan in uveal disease has been reported. A phase II study was therefore undertaken to assess the objective response rate of the combination of dacarbazine and treosulfan in previously untreated patients with metastatic uveal melanoma. All patients received dacarbazine 850 mg/m and treosulfan 8 g/m every 21 days up to a maximum of six cycles. Fifteen patients enrolled in the study. As expected, the major toxicities were haematological (particularly thrombocytopaenia) but the treatment was generally well tolerated. No responses were seen; however, disease stabilization was achieved in two patients. Median progression free survival from the start of chemotherapy was 12 weeks and median overall survival was 30 weeks. This study, using the combination of dacarbazine and treosulfan, while well tolerated, did not confirm earlier reports suggesting treosulfan is active in uveal melanoma.

Lung Cancer 2006 May 20; (Read article online)

Kakolyris S, Agelidou A, Androulakis N, Tsaroucha E, Kouroussis C, Agelidou M, Karvounis N, Veslemes M, Christophylakis C, Argyraki A, Geroyianni A, Georgoulias V

PURPOSE: To evaluate the efficacy and tolerance of a cisplatin plus etoposide regimen followed by thoracic radiotherapy (TRT) and paclitaxel plus cisplatin consolidation chemotherapy in patients with limited stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-nine patients with limited SCLC were enrolled onto this study. Patients received three courses of cisplatin 75mg/m(2) IV, day 1 and etoposide 100mg/m(2) IV, days 1-3 (EP regimen), followed by TRT (45-56Gy administered in 15 fractions), and three courses of paclitaxel 175mg/m(2) IV, day 1 and cisplatin, as previously, on day 2 (PP regimen); cycles were repeated every 21 days. RESULTS: All patients were evaluable for toxicity and 34 for response. The overall response rate was 67% (CR: 26%; PR: 41%; intention-to-treat analysis) (95% CI: 53.0-84.2%). After a median follow-up period of 15 months, the median survival time was 15 months, the median time to tumor progression 8.3 months and the 1-year survival rate 53.8%. Grade 3/4 neutropenia occurred in 39% and 36% of patients receiving EP and PP regimens, respectively. The incidence of febrile neutropenia was 5% and 3% for EP and PP regimens, respectively. Other hematologic and non-hematologic toxicities were mild, with the exception of esophagitis occuring in 36% of patients during and/or immediately after radiotherapy. CONCLUSION: Consolidation therapy with PP after sequential EP and thoracic radiotherapy is feasible and well-tolerated; however, the efficacy results are comparable with those previously obtained in the same patients' population using a combination of EP and TRT.

J Antimicrob Chemother 2006 May 22; (Read article online)

Coronado X, Zulantay I, Rozas M, Apt W, Sánchez G, Rodríguez J, Ortiz S, Solari A

OBJECTIVES: The aim of this work was to study the distribution of Trypanosoma cruzi clones after treatment failure with itraconazole or allopurinol in infected humans. METHODS: Blood samples from treated and untreated individuals were used to detect T. cruzi by PCR assays and were confirmed by hybridization tests using total kinetoplast DNA as a universal probe. Also, xenodiagnosis (XD) tests were performed with Triatoma infestans fed from the same group of patients. We performed Southern-blot analyses of PCR products from blood or XD samples using a panel of four genotype-specific probes: corresponding to T. cruzi clones TcI, TcIIb, TcIId and TcIIe. The membranes were hybridized with radiolabelled probes and exposed in a Personal Molecular Imager. RESULTS: When comparing the presence of T. cruzi clones in the allopurinol-treated group with the non-treated group significant differences were only observed for XD samples. Clone TcI was present in 9/13 (69.2%) of the XD samples of the treated group, but only in 8/27 (29.6%) in the non-treated group (P = 0.0178). When the itraconazole-treated group and the control group were compared, significant differences were found in both the blood and XD samples. In blood, the clone TcIIb was detected in 6/17 (35.5%) of the treated group and in 18/27 (66.7%) of the non-treated group (P = 0.0207). When XD samples were analysed, the clone TcI was observed in 14/17 (82.3%) of the itraconazole-treated group but only in 8/27 (29.6%) of the control group (P = 0.0006), which suggests resistance of this clone to itraconazole. CONCLUSIONS: We detected a dissimilar distribution of T. cruzi clones in treated and untreated groups of patients. The presence of TcI increased in patients treated with allopurinol and itraconazole, whereas the presence of TcIIb decreased in itraconazole-treated patients. The type of T. cruzi clone that prevails suggests that TcI is resistant to both drugs and that TcIIb is susceptible to itraconazole.

J Clin Oncol 2006 May 22; (Read article online)

Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM

PURPOSE: To update the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology. Update Methodology: The Update Committee completed a review and analysis of data published from 1998 thru February 2006. The literature review focused on published randomized controlled trials, and systematic reviews and meta-analyses of published phase II and phase III randomized controlled trials. Recommendations: The three-drug combination of a 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy of high emetic risk. For persons receiving chemotherapy of high emetic risk, there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics. These agents should be reserved for patients intolerant of or refractory to 5-HT3 serotonin receptor antagonists, neurokinin-1 receptor antagonists, and dexamethasone. The three-drug combination of a 5-HT3 receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide. For patients receiving other chemotherapy of moderate emetic risk, the Update Committee continues to recommend the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis. The Update Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk. CONCLUSION: The Update Committee recommends that clinicians administer antiemetics while considering patients' emetic risk categories and other characteristics.

World J Gastroenterol 2006 May 28; 12(20): 3253-8 (Read article online)

Ariyan CE, Salem RR

Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.

J Clin Oncol 2006 May 22; (Read article online)

Gaynon PS, Harris RE, Altman AJ, Bostrom BC, Breneman JC, Hawks R, Steele D, Zipf T, Stram DO, Villaluna D, Trigg ME

PURPOSE: To compare conventional sibling bone marrow transplantation (CBMT), BMT with alternative donor (ABMT), and chemotherapy (CT) for children with acute lymphoblastic leukemia (ALL) and an early first marrow relapse. PATIENTS AND METHODS: After informed consent, 214 patients with ALL and early marrow relapse began multiagent induction therapy. One hundred sixty-three patients with fewer than 25% marrow blasts and count recovery at the end of induction (second remission [CR2]) were allocated by donor availability. Fifty patients with sibling donors were allocated to CBMT. Seventy-two patients were randomly allocated between ABMT and CT while 41 patients refused allocation. RESULTS: Overall, 3-year event free survival from entry is 19% +/- 3%. Thirty-two of 50 CBMT patients (64%) and 19 of 37 ABMT patients (51%) underwent transplantation in CR2 with 3-year disease-free survival of 42% +/- 7% and 29% +/- 7%. The 3-year DFS is 29% +/- 7%, 21% +/- 7%, and 27% +/- 8% for patients allocated to CBMT, ABMT, and CT, respectively. Contrary to protocol, 12 of 35 patients allocated to CT underwent BMT in CR2. Of these, five patients died after BMT and 5 patients relapsed. CONCLUSION: More than one half of patients died, failed reinduction, or relapsed again before 3 months after CR2 (median time to BMT). Intent-to-treat pair-wise comparison of ABMT with CT, CT with CBMT, and CBMT with ABMT yields hazards of 1.2, 1.1, 0.8 with P values of .56, .80, and .36, respectively. Outcomes remain similar and poor for children with ALL and early marrow relapse. BMT is not a complete answer to the challenge of ALL and early marrow relapse.

Melanoma Res 2006 Jun; 16(3): 263-265 (Read article online)

Lejeune FJ, Monnier Y, Rüegg C

Experimental and clinical evidence indicates that non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors may have anti-cancer activities. Here we report on a patient with a metastatic melanoma of the leg who experienced a complete and sustained regression of skin metastases upon continuous single treatment with the cyclooxygenase-2 inhibitor rofecoxib. Our observations indicate that the inhibition of cyclooxygenase-2 can lead to the regression of disseminated skin melanoma metastases, even after failure of chemotherapy.

J Immunol 2006 Jun 1; 176(11): 6631-6639 (Read article online)

Condomines M, Quittet P, Lu ZY, Nadal L, Latry P, Lopez E, Baudard M, Requirand G, Duperray C, Schved JF, Rossi JF, Tarte K, Klein B

High-dose cyclophosphamide (Cy) and G-CSF are widely used to mobilize hemopoietic stem cells for treating patients with high-dose chemotherapy and autologous stem cell transplantation (ASCT). Because lymphocyte count in the graft collected after Cy-G-CSF treatment is an independent survival factor after ASCT for patients with multiple myeloma, our purpose was to study how Cy-G-CSF treatment affects the phenotype and function of T cells in patients with multiple myeloma. Cy induced a 3-fold decrease of T cell counts with a slow and partial T cell recovery of one-third at the time of hemopoietic stem cell collection. Cy-G-CSF treatment did not affect the relative ratios of central memory, effector memory, and late effector CD4(+) or CD8(+) T cells, but a decrease in the percentage of naive CD4(+) cells was observed. The percentages of CD25(+) cells increased 2- to 3-fold in CD4(+) and CD8(+) T cells, the former including both activated CD25(low) and CD25(high) cells. CD4(+)CD25(high) cells were regulatory T cells (Treg) that expressed high levels of FOXP3, CTLA-4, and GITR and displayed in vitro suppressive properties. The recovery of Treg absolute counts after Cy-G-CSF treatment was higher than the recovery of other lymphocyte subpopulations. In conclusion, Cy-G-CSF treatment induces a severe T cell count decrease without deleting Treg, which are potent inhibitors of antitumor response. The present data encourage novel therapeutic strategies to improve T cell recovery following ASCT while limiting Treg expansion.

Nucl Med Commun 2006 Jun; 27(6): 481-487 (Read article online)

Torizuka T, Nakamura F, Takekuma M, Kanno T, Ogusu T, Yoshikawa E, Okada H, Maeda M, Ouchi Y

OBJECTIVE: For surgical planning of uterine corpus cancer, prior knowledge of the depth of myometrial invasion is important. Curative tumour resection is possible in superficial invasion (stages IA and IB), while post-surgical chemotherapy or radiation therapy is required in deep invasion (stage IC). We evaluated the value of positron emission tomography with 2-[F]fluoro-2-deoxy-D-glucose (FDG PET) for estimating the myometrial invasion in uterine corpus cancer. METHODS: We studied 22 patients with clinical stage I uterine corpus cancer, who underwent FDG PET prior to surgery. Standardized uptake value (SUV; tracer activity per injected dose normalized to body weight) was calculated on the PET image. PET findings were compared with magnetic resonance imaging (MRI) and the surgical staging. RESULTS: The surgical stage was IA in five, IB in 11 and IC in six patients. SUVs in deep invasion (15.69+/-4.73, 8.83-21.84) were significantly higher than those in superficial invasion (9.09+/-3.29, 2.68-15.41) (P<0.005). Using 12.0 as a cut-off value of SUV for the differentiation of these two groups, PET results were correct in 19 patients but were incorrect in three patients. Although both PET and MRI provided correct staging in 14 patients, only MRI overestimated the myometrial invasion in four patients with stage IB and showed inconclusive findings in one patient with stage IC. Four of these five patients were post-menopausal. CONCLUSIONS: The cut-off value of SUV (=12.0) may be a useful index for the differentiation of superficial invasion and deep invasion. FDG PET may be feasible for predicting the myometrial infiltration of uterine corpus cancer, especially when uterine atrophy makes it difficult at MRI in post-menopausal patients.