Gemcitabine and carboplatin: is this the best combination for non-small cell lung cancer?

Approximately 30-40% of non-small cell lung cancer patients will present with metastatic disease, and its associated poor prognosis. Chemotherapy has an established palliative role within late-stage disease, but is also being used increasingly in the neoadjuvant and adjuvant settings. Platinum-based chemotherapy has been shown to produce definite improvements in efficacy and quality of life in non-small cell lung cancer patients, and is now the standard of care. Carboplatin has similar biochemical properties to those of cisplatin. However, carboplatin has much less renal, otologic, neurologic and upper gastrointestinal toxicities than cisplatin, and treatment can be conveniently delivered in an out-patient setting. Furthermore, platinum combinations with third-generation cytotoxics have shown additional gains in survival rates. Gemcitabine and carboplatin is a well-tolerated regime. Recent meta- and cost analyses have discovered that gemcitabine-based regimes may have an advantage over other third-generation agent platinum combinations. This article reviews the evidence demonstrating that gemcitabine-carboplatin is effective, convenient and cost effective.     

Measuring psychosocial outcomes: is the consumer or the professional the best judge?

In this review, we explore professionally‐driven and consumer‐driven paradigms in measuring psychosocial outcomes for cancer care. Early measures of psychosocial well‐being focussed on clinically‐derived concepts of dysfunction. Recent literature reflects a paradigm shift toward a consumer‐driven approach to the conceptualisation and measurement of psychosocial well‐being. The key distinction between the two approaches rests on whether the professional or consumer retains judgement authority and raises the question of whether it is necessary to include both perspectives in research and practice. Research is proposed to clarify our interpretation of these approaches with a view to devising novel interventions to benefit patient well‐being.     

What is the best schedule for administration of gemcitabine-taxane?

Until recently, standard adjuvant chemotherapy for metastatic breast cancer (MBC) consisted of anthracycline-based regimens, followed by a taxane. However, data suggest that taxane-based combinations can be more effective than taxanes alone for the second part of treatment. Synergy between paclitaxel and gemcitabine was demonstrated in vitro when paclitaxel was followed by gemcitabine. Dose-dense regimens administered every 2 weeks are more effective than standard 3 weekly regimens. In a phase II study, gemcitabine plus paclitaxel every 2 weeks as first-line chemotherapy of MBC was associated with an overall response rate (ORR) of 71%. Women with HER2 ECD-positive tumours have a poor ORR (40%) to first-line chemotherapy. The addition of trastuzumab to dose-dense paclitaxel-gemcitabine as first-line chemotherapy in women with HER2-positive MBC was associated with a dramatic increase in ORR to 78%, with no serious toxicity observed. Two phase III clinical trials of gemcitabine-paclitaxel as adjuvant chemotherapy in women with histologically-confirmed MBC are currently underway. Preliminary data show that this drug combination is well-tolerated, and the efficacy results are eagerly awaited.     

What is the best test to detect prostate cancer?

The data accumulated during screening of these 300 men suggest that the digital rectal examination is the most efficient test for the diagnosis of prostate cancer. This test is universally available, because physicians believe that it should routinely be performed as part of the physical examination of every man, particularly for men over the age of 40. The digital rectal examination provides useful clinical information about the rectum, anal sphincter, and the quality of stool. Its diagnostic accuracy is unexcelled by more recent, complex, and expensive tests. Finally, in this age of escalating medical costs and physician accountability for these costs, you can't beat the price of the digital rectal examination.     

Anal cancer: is neoadjuvant cisplatin chemotherapy or chemoradiotherapy friend or foe?

This Practice Point commentary discusses the findings of the Intergroup RTOG 98-11 trial, which aimed to investigate both the potential role of cisplatin as neoadjuvant chemotherapy, and also its role concurrently in combination with radiotherapy, for anal-canal carcinoma. Although chemoradiotherapy has had an important effect on the treatment of anal cancer, and allows preservation of anorectal function with survival rates similar to or better than those of surgical treatment, overall survival rates for advanced tumors are still in the region of 50-60% at 5 years. A strong theoretical rationale for cisplatin-based treatment in anal cancer exists; several phase II trials have demonstrated a high response rate with reduced colostomy rates. The Intergroup results are disappointing in that neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, followed by cisplatin-based chemoradiotherapy did not improve overall survival, disease-free survival and locoregional control when compared with the standard treatment of combined 5-fluorouracil and mitomycin chemoradiotherapy.     

Three-dimensional conformal external beam radiotherapy or brachytherapy: which is the "best alternative" to radical prostatectomy?

The choice of treatment for clinically organ-confined prostate cancer is complicated by the fact that there are no studies demonstrating the clear superiority of one option. As a radiation oncologist who performs both external beam radiotherapy and brachytherapy, Dr. Roach provides a fascinating and balanced perspective on how he views the selection process, as well as how he approaches a decision.     

Chronic myeloid leukemia in the tyrosine kinase inhibitor era: What is the best therapy?

Imatinib mesylate, 400 mg/d, is considered standard therapy for managing patients with chronic myeloid leukemia (CML) in chronic phase, yielding high rates of cytogenetic responses that translate into favorable long-term outcomes. However, some patients do not achieve adequate levels of response, lose a previously acquired response, or are forced to discontinue imatinib therapy because of safety reasons. To avoid these outcomes, several approaches are being tested in the frontline setting, including the use of higher imatinib doses or second-generation tyrosine kinase inhibitors such as nilotinib or dasatinib, the latter of which is approved only for managing patients who have imatinib therapy failure. Newer multikinase inhibitors active against multiple ABL1 mutations are also under development for patients in any CML phase who have therapy failure on sequential imatinib and a second-generation tyrosine kinase inhibitor or carry the highly resistant T315I mutation and are not candidates for allogeneic stem cell transplantation. Some of these approaches are expected to improve the outcomes of patients with CML.     

Nuclear or cytoplasmic expression of survivin: What is the significance?

Growing evidence suggests that survivin expression in cancer cell nuclei may represent an important prognostic marker to predict disease outcome for cancer patients. Current reports in this research area, however, are inconsistent and propose opposing conclusions regarding the significance and prognostic value of survivin nuclear expression. The aim of our study is to review and discuss the data reported in the original publications. We have also provided new experimental data to support our view regarding the possible reasons for the observed inconsistencies in the literature. This would alert researchers to pay attention to potential pitfalls in the determination of nuclear or cytoplasmic expression of survivin for the future.     

Pharmacokinetics of (glycolato-0,0′)-diammine platinum (II), a new platinum derivative,in comparison with cisplatin and carboplatin

Summary The pharmacokinetics of (glycolato-0,0)-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m², respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 g/ml and 959 g/min per ml for 254-S, 3.09 g/ml and 208 g/min per ml for cisplatin, and 19.90 g/ml and 3446 g/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.     

What is the best treatment for children with limited-stage Hodgkin lymphoma?

Limited-stage Hodgkin lymphoma remains a challenging problem for pediatric oncologists. Published and investigative treatment regimens represent varied approaches to balance the excellent overall and event-free survival with the substantial potential for long-term sequelae of effective treatment modalities. Regimens incorporating low-dose radiation to smaller fields and chemotherapy that limits cumulative exposure to the agents most closely associated with long-term complications have been shown to be effective for most patients. Investigative approaches to optimize overall therapy focus on identifying which patients require more or less therapy. A recent example is the use of response-based therapy as a means of limiting or omitting radiation for those with an early, rapid response to chemotherapy. Biologic markers that influence risk for treatment failure or treatment-related toxicities have been only minimally defined. This paper reviews recently published treatment regimens for children and adolescents and presents some considerations for choosing a treatment approach for individual patients.     

Well-differentiated neurocytoma: what is the best available treatment?

Most neurocytomas are well differentiated, being associated with better long-term survival than the more aggressive atypical lesions. Atypical neurocytomas are characterized by an MIB-1 labeling index >3% or atypical histologic features. This analysis focuses on well differentiated neurocytomas in order to define the optimal treatment. A case with a follow-up of 132 months is presented. The patient developed two recurrences two and four years after first surgery, each showing an increasing proliferation activity. Furthermore, all published well-differentiated neurocytoma cases were reviewed for surgery, radiotherapy, and prognosis. Additional relevant data were obtained from the authors. Complete resection (CTR), complete resection plus radiotherapy (CTR + RT), incomplete resection (ITR), and incomplete resection plus radiotherapy (ITR + RT) were compared for outcome by using the Kaplan-Meier method and the log-rank test. Data were complete in 301 patients (CTR, 108; CTR + RT, 27; ITR, 81; ITR + RT, 85). Local control and survival were better after CTR than after ITR (P < 0.0001 and P = 0.0085, respectively). Radiotherapy improved local control after ITR (P < 0.0001) and after CTR (P = 0.0474), but not survival (P = 0.17 and P = 1.0, respectively). In the ITR + RT group, doses < or =54 Gy (n = 33) and >54 Gy (n = 32) were not significantly different for local control (P = 0.88) and survival (P = 0.95). The data demonstrated CTR to be superior to ITR for local control and survival. After CTR and ITR, radiotherapy improved local control, but not survival. A radiation dose of 54 Gy appeared sufficient. Application of postoperative radiotherapy should be decided individually, taking into account the risk of local failure, the need for another craniotomy, and potential radiation toxicity.     

What is the best treatment modality for adrenal metastasis from hepatocellular carcinoma?

PURPOSE: This study aimed to analyze the effect of each therapeutic modality to clarify the treatment strategy for adrenal metastases from hepatocellular carcinoma (HCC). METHODS: Adrenal metastasis from HCC was observed in 45 patients. Fifteen patients who were determined to have multi-organ metastasis including the adrenal glands were excluded, and the remaining 30 patients were reviewed. RESULTS: The location of adrenal metastasis was right side, left side, and both in 17, 9, and 4 patients, respectively. Treatment for adrenal metastasis consisted of adrenalectomy in 5 patients, non-surgical treatment such as TACE, or chemotherapy and radiotherapy in 19 patients, while 6 patients received no treatment. The median survival duration was 11.05 months in the 30 patients with adrenal metastasis. In the 25 patients with well-controlled intrahepatic lesions, the median survival time of those patients who received adrenalectomy, non-surgical treatment, and no treatment was 21.41, 11.05, and 5.64 months, respectively. The difference in cumulative survival according to mode of treatment of adrenal metastasis in the well-controlled intrahepatic lesion group was statistically significant. CONCLUSION: We envisage increased benefit after adrenalectomy in terms of survival in patients with well controlled intrahepatic lesions at the time of adrenal metastasis and good general medical condition.     

What is the best position of the arms in mantle field for Hodgkin's disease?

PURPOSE: To evaluate the best position of the arms in mantle field for Hodgkin's disease. METHODS AND MATERIALS: In 12 patients, with surgical clips placed at the time of an axillary dissection for breast cancer, the radiological projection of the clips according to three arm positions was prospectively evaluated: akimbo (A), extended (E), and up over the head (U). The surgical clips were arbitrarily separated into two groups: lower and upper. In each patient, the distance between the surgical clips and chest wall was measured, and the possibility of shielding the lungs and humeral heads was evaluated. RESULTS: The mean displacement of the lower clips away from the chest wall when the patients were in A, E, and U positions was 2.5, 3.0, and 4.6 cm, respectively. The upper group clips showed a lower difference in distance from chest wall. In the U position, there was always a clip of the lower group that projected over the humeral head, making it impossible to block this structure. CONCLUSION: In the A position, there is the possibility of blocking the humeral head, but it is necessary to irradiate more lung parenchyma. Type E treatment setup allows the shielding of both lung and humeral head, while maintaining adequate margins around the axillary nodes. In the U position, there is a greater possibility of shielding the lung parenchyma, but it is impossible to block the humeral heads.     

Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?

Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4) used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1) and good renal function–glomerular filtration rate (GFR) >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4) bladder cancer.