Courses Of Standard Chemotherapy Research Articles

A multicenter randomized phase II (rPII)/III study comparing concurrent chemoradiotherapy (CRT) with low-dose cisplatin plus continuous infusion of 5-fluorouracil (LDPF) and standard-dose PF (SDPF) for locally advanced unresectable squamous cell carcinoma of the thoracic esophagus (JCOG0303).

4053 Background: Cisplatin-based CRT is one of the standard treatments for locally advanced unresectable esophageal carcinomas. Although both cisplatin and 5-FU are known to enhance the efficacy of radiotherapy, the optimal chemotherapy regimen has not been established. Thus, we evaluated CRT with LDPF on effectiveness and adverse events for locally advanced unresectable esophageal carcinomas in a randomized study to determine if it is an acceptable alternative to SDPF. Methods: Eligibility criteria included histologically proven squamous cell, adenosquamous, or basaloid carcinoma; tumor located in thoracic esophagus; and definite T4 and/or unresectable regional lymph node metastasis. In arm A, two courses of standard chemotherapy of cisplatin (70 mg/m2, div day1, 29) plus 5-FU (700 mg/ m2, ci day1-4, 29-32) were given with external beam radiation (EBRT) in 30 daily fractions, 5 d/week to a total dose of 60 Gy. In arm B, low dose daily cisplatin (4 mg/ m2, div) plus 5-FU (200 mg/ m2, ci) was administered on the same days that EBRT was given. The primary endpoint was overall survival (OS). The rPII study was designed to evaluate the efficacy of LDPF to decide whether it warranted a phase III trial. Results: Between Apr. 2004 and Jun. 2009, 135 pts (Arm A/B; 67/68) from 40 institutions were randomized. Tumor depth (T1-3/T4) was 18/49 in arm A and 13/55 in arm B. The median follow-up time for all eligible pts was 9.9 mos. Toxicities were almost equivalent in both arms; however LDPF necessitated long hospitalization. Moreover, the OS of pts of LDPF group was slightly inferior to that of those treated with SDPF (hazard ratio, 1.048, 95%CI, 0.782-1.045; median OS (A/B), 13.0/13.6 mos.; 3-year OS (A/B), 30/26%). Because of the inferior efficacy of LDPF, the Data and Safety Monitoring Committee of the JCOG recommended the termination of the study at the end of rPII. Conclusions: CRT with LDPF is not recommended for pts with locally advanced unresectable esophageal cancer. No significant financial relationships to disclose.

Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: A randomised phase II study

Background The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity accompanying standard cisplatin-based chemotherapy in patients with epithelial ovarian cancer (EOC). Patients and methods A double-blind, placebo-controlled, randomised study was conducted in which study arm magnesium sulphate (5 g) was administered before each course of standard chemotherapy with paclitaxel (135 mg/m 2/24 h) plus cisplatin (75 mg/m 2) every 3 weeks in patients with EOC. Magnesium subcarbonate (500 mg), three times per day orally, was administered during the treatment intervals. The control arm was administered a placebo instead of both magnesium salts. Magnesium serum levels (sMg) and GFR markers: serum levels of creatinine (sCr), Cockroft–Gault (ClCG) and Modification Diet of Renal Disease (MDRD) formulae were recorded before each cycle, and 3 weeks after the sixth course. Results 41 EOC patients were randomised and 40 were eligible. sMg varied significantly between the supplemented and placebo groups ( p<0.0001). The control group showed a significantly greater decrease of GFR assessed by: sCr ( p = 0.0069), ClCG ( p = 0.0077) and MDRD ( p = 0.032) formulae compared with the magnesium supplemented group. Conclusions These results demonstrate the nephroprotective effect of magnesium supplementation during chemotherapy with cisplatin.

Nephroprotective role of magnesium salt in cisplatin-induced renal damage in patients with ovarian cancer

16532 Background: Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage. The experimental studies indicate a substantial additive effect of Mg- depletion on cisplatin induced renal toxicity. The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity after giving the standard cisplatin- based chemotherapy in patient with epithelial ovarian cancer (EOC). Methods: A double-blind, placebo- controlled, randomised study conducted in which magnesium sulphate was administered at a dose of 5 g as an iv infusion before each of course of standard chemotherapy with paclitaxel 135 mg/m2 over 24 h infusion plus cisplatin 75 mg/m2 (PP) every 3 weeks in patients with EOC. Between each of courses and 3 weeks after six of this regiments the patients were administered magnesium subcarbonate at a dose 500 mg three times per day p.o. GFR markers as: serum levels of creatinine, creatinine clearance estimated on Cocroft- Gault (ClCG) and Modification Diet of Renal Disease (MDRD1) formula were recorded before the starting each of the cycles, and 3 weeks after the sixth course. Results: Between January 2003 and January 2006, 41 EOC patients who underwent randomization, 40 were eligible. We noted that serum levels of magnesium significantly varied between supplemented and non- supplemented groups (p<0.0001). The placebo (control) group showed significantly greater slope of GFR assessed by: serum levels of creatinine (p=0.0069), creatinine clearance estimated on Cocroft- Gault (p=0.0077) and MDRD1 (p=0.032) formula than magnesium supplemented group. Neither group showed differences in tumor growth rates or outcome. Conclusions: These results show that magnesium supplementation during chemotherapy with Cisplatin/ Paclitaxel is a nephroprotective management with no reduction of antitumor efficacy. No significant financial relationships to disclose.

Testicular tumors

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.

Advanced Stage Hodgkin Lymphoma: The Predictive Value on Treatment Outcome of Early FDG-PET Scan Is Independent of and Superior to IPS Score.

Background: FDG-PET scan performed early during chemotherapy (CT) is a powerful prognostic tool in lymphoma management. This study aimed to compare the predictive value on treatment outcome of the International Prognostic Score (IPS) with that of FDG-PET scan performed after two courses of standard CT in untreated advanced stage (AS) HL patients.Patients: From December 2001, 202 new AS HL patients were consecutively admitted to 11 Italian and 3 Danish hematological centers, on behalf of Intergruppo Italiano Linfomi and Danish Lymphoma Cooperative Group. The mean age was 35.5 years (14–79), the male/female ratio 105/97; AS (IIB–IVB) was present in 153, and unfavorable stage IIA (> 3 nodal sites involved or sub-diaphragmatic presentation or bulky disease or ESR > 40) in 49. Bulky and extranodal disease was recorded in 71 and 58 patients, respectively. All patients had FDG-PET at baseline (PET-0) and after 2 courses of CT (PET-2). 192 patients were treated with ABVD, 8 with ABVD-like CT, 2 with BEACOPP. 102 patients received consolidation radiotherapy after CT. All patients were given the therapy programmed at baseline, except in case of overt progression.Results: The mean time from the diagnosis to latest follow-up was 796 days (range 91–1716). 164 patients attained CR while 38 were chemoresistant: 34 showed disease progression during CT and 4 showed early relapse (within 6 months) after CR entry: (+28 – +178 days). 4 out of the 164 pts attaining CR relapsed later than 6 months. In univariate analyses, both PET-2 (p<0.0001) and IPS (p<0.001) were significantly associated with a higher probability of treatment failure. However, in a multivariate analysis only PET-2 was independently predictive of relapse/progression probability (51.0; 95 % C.I. 20.9 – 124.2). The sensitivity of PET-2 for treatment failure was 85%, the specificity 96% and the overall accuracy 94%. The 2-y FFS probability for PET-2 negative and for PET-2 positive patients were 96% and 14%, respectively (log Rank test, p<0.0001; Fig. 1).Conclusions: so far, FDG-PET after two cycles of CT is the most powerful tool available for predicting treatment outcome in AS HL. [Display omitted]

Detailed Nodal Features of Cervical Tuberculous Lymphadenitis on Serial Neck Computed Tomography Before and After Chemotherapy

To investigate the relation between clinical outcomes and nodal features on computed tomography (CT) in cervical tuberculous lymphadenitis (CTBL) before and after antituberculous chemotherapy. Fifty-six patients with CTBL underwent CT before and after a 6- or 12-month course of standard chemotherapy. Three radiologists evaluated the nodal features on serial CT retrospectively, including calcification (no/punctuate/large), necrosis (no/eccentric/central), perinodal infiltrations (no/localized/extensive), and enhancing patterns (no/peripheral/homogeneous). The clinical outcome was defined as "favorable" (n = 33) or "unfavorable" (n = 23) at the completion of chemotherapy. All the features on the initial CT scan did not show a statistically significant difference between the favorable and unfavorable groups. On the final CT scan, absence of necrosis (P < 0.005), no infiltration (P < 0.005), no enhancement (P < 0.008), and central enhancement (P < 0.014) were more common in the favorable group, whereas large necrosis (P < 0.005), localized and extensive infiltration (P = 0.005, P < 0.005), and peripheral enhancement were more common in the unfavorable group (P < 0.005, P = 0.009). Central necrosis, perinodal infiltration, and peripheral rim enhancement on the final CT scan showed differences between the 2 groups. These CT features reflecting inflammation can be useful findings for assessing treatment response.

Lung Resection for Multidrug-Resistant Tuberculosis

The emergence of multidrug-resistant tuberculosis poses a serious challenge to traditional drug therapy. In view of the relapse rate of up to 50% following medical management, there has been renewed interest in the role of surgery for this problem. We report our experience with lung resection for this condition. Over a 5-year period, resection was performed in 23 patients who were diagnosed with multidrug resistance after completing a course of standard chemotherapy and at least 3 months of second-line therapy. Pneumonectomy was performed in 17 patients and lobectomy in 6. There was no operative or postoperative mortality. Major complications developed in 4 patients (17.4%): 2 had post-pneumonectomy empyema and 2 underwent rethoracotomy for bleeding. Ten patients were sputum positive preoperatively, and only 1 remained positive after surgery. The patients were put on appropriate chemotherapy and followed up for 18 months. The cure rate was 95.6%. Pulmonary resection can be considered as an important adjunct to medical therapy in carefully selected patients: those who have localized disease with adequate pulmonary reserve, or who have multiple previous relapses, or whose sputum remains positive after 4 to 6 months of appropriate medical treatment. Surgery offers high cure rates with acceptable morbidity and mortality.

Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up

AbstractShortly before the all-transretinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m2 IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m2 IDA daily for 4 days combined with 200 mg/m2 Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P = .0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P = .0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/μL (P = .0001) and increasing age (P = .0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.

Cytomegalovirus Colitis--A Severe Complication after Standard Chemotherapy

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.

Use of thrombopoietic growth factors in acute leukemia.

Several hematopoietic growth factors have been shown to affect megakaryocyte development, and two, interleukin (IL)-11 and thrombopoietin (TPO) are presently being evaluated for use in patients with thrombocytopenia. In two studies patients who required one or more platelet transfusions during their first course of chemotherapy were found to require fewer platelet transfusions if their second cycle was augmented with IL-11. The drug was generally safe, with cardiovascular compromise the only significant complication occurring in a minority of patients. Although these reports included patients with various malignancies, studies of IL-11 in patients with myeloproliferative disorders have not been presented. In several clinical trials in cancer patients treatment with TPO was safe, and when administered early following a moderately aggressive cytotoxic insult was effective in accelerating platelet recovery. In addition, in both pre-clinical and clinical trials, TPO given to stem cell donors during mobilization lead to accelerated hematopoietic recovery. Finally, TPO appears safe when administered to patients with acute myelogenous leukemia (AML), both with respect to acute toxicity and long-term outcome of the leukemia. However, when used following a 7-day course of standard chemotherapy, the agent does not appear to accelerate platelet recovery. As such, additional clinical trials to test different growth factor regimens are ongoing. A number of studies have suggested that megakaryocytic growth factors may play a role in the biology of myeloproliferative disorders. Given the potential for adversely affecting patients with these disorders, the affects of IL-11 or TPO in patients with AML must continue to be carefully studied.

Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies.

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma (n = 148), Hodgkin's disease (n = 22) and multiple myeloma (n = 30). The variables predicting the collection of a minimal (>2.5 x 10(6)/kg) or a high (>10 x 10(6)/kg) CD34+ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy (n = 49) or high-dose cyclophosphamide, given alone (n = 55) or combined with high-dose VP16 (n = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34+ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count (P=0.06 and 0.0008 respectively). The target to collect a high CD34+ cell count was negatively associated with the number of previous chemotherapy regimens (P=0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield (P=0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.

Tuberculosis of the breast

The case histories of five women patients with mammary tuberculosis are described. All were treated by surgical excision of the lesion followed by antituberculosis chemotherapy. Recovery was uncomplicated in four of the patients but the fifth had a recurrence after 6 months for which a second operation was required. Tuberculosis of the breast is rarely diagnosed by clinical methods alone. The main problem is to distinguish it from pyogenic abscess in young women and from mammary carcinoma in older women. Surgical excision is often needed to prove the diagnosis. All patients should be given a standard course of chemotherapy but the value of surgery in the treatment of this disease has yet to be assessed.