Is there a preferred combination chemotherapy regimen for metastastic non-small cell lung cancer?

Since over 70% of patients with non-small cell lung cancer (NSCLC) have advanced (locally advanced or metastatic) disease, the majority of NSCLC patients might benefit from chemotherapy. During the past decade, a number of new agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan) have been found to be effective against lung cancer. These agents have been combined with cisplatin, carboplatin, and nonplatinum drugs to treat NSCLC. They, in general, produce median survival times of 8-10 months and 1- and 2-year survival rates of 35%-40% and 10%-15%, respectively. Based on this review, there is not a preferred combination chemotherapy regimen to treat advanced NSCLC patients. However, there are a number of different regimens from which to choose.     

Is there place for radiotherapy in the treatment of advanced ovarian cancer?

BACKGROUND AND PURPOSE: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. MATERIAL AND METHODS: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only. RESULTS: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. CONCLUSION: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.     

Is there a role for short-term hormone use in the treatment of nonmetastatic prostate cancer?

We reviewed our institution's experience treating patients with prostate cancer with 3-dimensional conformal radiation therapy (3DCRT) and short-term adjuvant hormonal therapy to determine biochemical no evidence of disease (bNED) and clinical outcome compared with patients treated with 3DCRT alone. Between 4/1/89 and 11/30/94, 558 patients with clinically localized prostate cancer received treatment at Fox Chase Cancer Center (Philadelphia, Pa.); 484 patients were treated with 3DCRT alone (Group I); 74 patients were treated with 3DCRT and hormones (Group II). Five-year actuarial rates of bNED control, distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were calculated for pretreatment PSA, Gleason score, T stage, use of hormones, treatment field size, age, and dose. A matched case/control analysis was performed to further evaluate the effect of hormones on treatment with 3DCRT. Median follow-up was 47 months (range: 2-97 months). The 5-year actuarial rates of bNED control, DMFS, CSS, and OS were 66%, 93%, 98%, and 86%, respectively, for Group I patients and 68%, 93%, 98%, and 89%, respectively, for Group II patients. Multivariate analysis demonstrated that hormone use was an independent predictor of bNED control only. A significant difference in bNED control was observed between Group I and II (43% vs. 71%) using the matched case/control analysis (P = 0.02). A trend towards significance was observed for different rates of DMFS between Group I and II (79% vs. 94%, P = 0.09). Patients with clinically localized prostate cancer with poor prognostic features (pretreatment PSA > or = 10 ng/ml, Gleason score > or = 7, and/or T2c or greater palpation stage) show improved rates of bNED control and a trend towards improved DMFS when treated with 3DCRT and short-term adjuvant hormones compared with 3DCRT alone. Long-term observation will be necessary to see if improvements in bNED control will translate into improvements in overall survival.     

Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials

BACKGROUND: Non-platinum regimens have been proposed as an alternative to the platinum-based combinations for treatment of advanced non-small cell lung cancer. However, conflicting results were reported. METHODS: Meta-analysis of phase III trials randomizing platinum-based versus non-platinum combinations as first-line chemotherapy with 1-year survival rate as a primary endpoint. Fourteen trials have been identified. Experimental arms were gemcitabine/vinorelbine (n=4), gemcitabine/taxane (n=7), gemcitabine/epirubicin (n=1), paclitaxel/vinorelbine (n=1), and gemcitabine/ifosfamide (n=1). The comparator was a doublet of a platinum compound plus a third generation agent for all but two studies (triplets). Updated data were available for 13 studies. The Peto and Yusuf method was used to generate odds ratios (OR). All tests are two-sided. RESULTS: A statistical heterogeneity was detected when the 13 studies were analyzed. Considering that current guidelines recommend platinum-based doublets as standard therapy we therefore limited the meta-analysis to the set of 11 phase III studies which used a platinum-based doublet (2298 and 2304 patients in platinum-based and non-platinum arms, respectively). No significant heterogeneity was detected in this consistent group of studies. Patients treated with a platinum-based regimen benefited from a statically significant reduction in the risk of death at 1 year (OR: 0.88, 95% CI 0.78-0.99; p=0.044) and a lower risk of being refractory to chemotherapy (OR: 0.87, 0.73-0.99; p=0.049). Forty-four (1.9%) and 29 (1.3%) toxic-related deaths were reported for platinum-based and non-platinum regimens, respectively (OR: 1.53; 0.96-2.49, p=0.08). An increased risk of grade 3-4 gastro-intestinal and hematological toxicity for patients receiving platinum-based chemotherapy was statistically demonstrated. There was no statically significant increase in risk of febrile neutropenia, OR=1.23 (0.94-1.60, p=0.063). CONCLUSION: A platinum-based doublet induced a statically significant reduction in the risk of death when compared with non-platinum chemotherapy without inducing an unacceptable increase in toxicity.     

Weekly taxane–anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer: a randomized controlled trial

Background: Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-basedchemotherapy on breast cancer. However, few studies have assessed the efficacy of weekly taxane–anthracyclineregimens on locally advanced breast cancer. This study was to compare the efficacy and safety of a weekly taxane–anthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breastcancer.Methods: Patients with locally advanced breast cancer were randomized to receive 4–6 cycles of neoadjuvant chemotherapywith tri-weekly 5-fluorouracil–epirubicin–cyclophosphamide (FEC) regimen or weekly paclitaxel–epirubicin(PE) regimen. The primary endpoint was the pathologic complete response (pCR) rate. Other endpoints included theclinical tumor response, breast-conserving surgery rate, and adverse events.Results: Between March 2010 and September 2013, 293 patients were randomized to the FEC (n = 151) and PE(n = 142) arms. The overall clinical response rate was significantly higher in the PE arm than in the FEC arm (76.06% vs.59.95%, P = 0.001). Consistently, the post-chemotherapy pathologic T and N stages were significantly lower in the PEarm than in the FEC arm (P < 0.001). However, the pCR rate was similar in the two arms (10.61% vs. 12.31%, P = 0.665).Overall, 36 (27.27%) patients in the FEC arm and 6 (35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms, with more severe neutropenia in the PE arm than in the FEC arm(11.97% vs. 5.96%, P = 0.031).Conclusions: In patients with locally advanced breast cancer, weekly PE was not superior to FEC in terms of pCR.However, weekly PE has a higher response rate and superior down-staging effects. On this account, the PE regimenmay be considered an alternative option for locally advanced breast cancer. Long-term follow-up data are needed toconfirm the efficacy of this regimen on locally advanced breast cancer.     

Is there a role of nab-paclitaxel in the treatment of advanced non-small cell lung cancer? The data suggest yes

Nab-paclitaxel is a novel therapeutic agent, which was approved in combination with carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) regardless of histologic subtype in the United States of America by the Food and Drug Administration in 2012 and by the European Commission in 2015. This approval was based on the results of a phase III clinical trial showing superior response rates compared with solvent-based paclitaxel in combination with carboplatin. This review will focus on the early development and clinical data to date supporting the use of nab-paclitaxel in advanced NSCLC. The clinical question central to this review is whether nab-paclitaxel has a place in the current therapeutic landscape of advanced NSCLC.     

Is there a standard chemotherapeutic regimen for hormone-refractory prostate cancer? Present and future approaches in the management of the disease

Prostate cancer that no longer responds to hormonal manipulation can be defined as hormone-refractory prostate cancer. Until recently, there has been no standard chemotherapeutic approach for hormone-refractory prostate cancer. The major benefits of chemotherapy in the treatment of the disease are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. Phase III studies are necessary to better evaluate the efficacy of the different regimens, because several old studies suffer for methodological deficits. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes. Phase I and II trial are testing combinations of classic chemotherapeutic agents and biologic drugs, and the first results appear interesting. In this article, recent advances in the treatment of hormone-refractory prostate cancer using chemotherapeutic regimens are critically reviewed.     

Is there a role for fractionated radiotherapy in the treatment of arteriovenous malformations?

Single fraction radiotherapy for the treatment of arteriovenous malformations (AVMs) is appropriate when brain tolerance is not a limiting factor, but when tolerance is a concern, there is a potential for therapeutic gain with fractionated treatment. alpha/beta values for AVM obliteration have been derived and found to be higher than previously assumed and are likely to be approximately 10.0 Gy or more compared with approximately 1.5 Gy for the tolerance of small volumes of brain. Models are derived to describe, qualitatively, the potential gain that can be achieved with fractionation. Past experience has identified an important volume effect that has limited the use of stereotactic treatments to small volumes. Volume-dependent, dose-volume relationships are described, including a tissue-specific volume exponent (phi) which was found to apply across a relatively wide range of target volumes, thereby permitting the derivation of tolerance guidelines to volumes larger than previously available. More data to define parameter values more precisely are desirable.     

Is there a role for intraperitoneal chemotherapy in the management of ovarian cancer?

Phase I and II clinical trial data have demonstrated the safety, pharmacokinetic advantage, and potential for enhanced cytotoxicity associated with the intraperitoneal administration of antineoplastic agents in the management of ovarian cancer. In two randomized phase III studies comparing the intraperitoneal and intravenous administration of cisplatin (Platinol) as initial therapy for small-volume residual advanced ovarian cancer, intraperitoneal delivery of the agent produced superior progression-free and overall survival. Reluctance to employ intraperitoneal cisplatin in the standard management of ovarian cancer appears to be related to the added time, effort, and potential morbidity associated with the approach, as well as a general preference for the less toxic, less complicated carboplatin (Paraplatin)-based regimen. However, existing data support the use of this unique method of drug delivery in carefully selected patients outside of the clinical trial setting.