Concurrent Combination Chemotherapy Research Articles

Management of Patients With Advanced Urothelial Carcinoma in an Evolving Treatment Landscape: A Qualitative Study of Provider Perspectives of First-Line Therapies.

The treatment landscape in locally advanced/unresectable or metastatic urothelial carcinoma (aUC) has evolved with the use of immune checkpoint inhibitors (ICIs) in the first line (1L) and platinum-refractory settings and with the recent approval of avelumab as 1L maintenance therapy for patients achieving disease control with platinum-containing regimens. Oncology provider perspectives and decision-making processes regarding aUC management, especially with the integration of recently approved strategies, such as maintenance therapy, have not been well-described. Qualitative interview study with US oncologists and oncology nurses in academic and community settings in August 2020. Interviews explored decision-making around aUC 1L treatment eligibility determinants and selection, programmed cell death 1 ligand 1 (PD-L1) testing practices, and use of maintenance therapy. Thematic analysis was used to identify drivers of 1L treatment decisions. Eighteen oncologists (women, 11%; >15 years in practice, 55%; academic, 39%) and 18 oncology nurses (women, 94%; >15 years in practice, 34%; academic, 50%) participated. Providers preferred platinum-based regimens in 1L setting and reserved 1L ICI monotherapy for frail patients. Providers preferred chemotherapy followed by switch maintenance ICI, as opposed to concurrent combination chemotherapy and ICI, followed by ICI as continuation maintenance. Decision-making was driven by need to adhere to treatment decision-making guidelines, characteristics of the patient, treatment efficacy and patient preference. Providers adhered to guidelines and level I evidence in decision-making in the aUC 1L setting. Future studies should further evaluate barriers to the adoption of standard-of-care strategies and factors impacting decision-making in the real-world setting.

Efficacy and safety of S-1 (tegafur, gimeracil, and oteracil potassium) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients

PurposeThis study evaluated the efficacy and safety of the combination drug tegafur, gimeracil, and oteracil potassium (S-1) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients. Patients and methodsPatients with pathologically or cytologically newly diagnosed lung squamous cell carcinoma (n=106) were randomly assigned to receive the combination of tegafur, gimeracil, and oteracil potassium (40mg/m2, BID, d1−28, repeated every 6 weeks for 4 cycles) and concurrent 3D-conformal radiotherapy (60Gy; experimental group), or gemcitabine (800−1000mg/m2, d1 and d8) repeated every 21 days for 4 cycles as well as 3D-conformal radiotherapy (control group). ResultsThe overall response rate (complete and partial responses) of the experimental group was 68.6%, which was significantly higher than that of the control group (38.5%; P=0.002). The median progression-free survival rates of the experimental and control groups were 11.8 months (95% confidence interval [CI]: 8.0−22.4) and 7.8 months (95% CI, 6.9–9.2), respectively (P=0.017). Adverse reactions included grade I/II radiation esophagitis and pneumonitis, with good tolerance. Grade III/IV adverse reactions of the experimental and control groups were leucopenia (20% cf. 56.6%, respectively; P=0.027), thrombocytopenia (3.9% cf. 25%; P=0.037), and gastrointestinal reaction (1.9% cf. 3.5%; P=0.35). ConclusionThe efficacy of concurrent combination chemotherapy with tegafur, gimeracil, and oteracil potassium (S-1) and 3D-conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients was excellent, and all toxicities were well tolerated. This treatment might be considered a main regimen in the management of squamous cell carcinoma of the lung in elderly patients.

Myelodysplastic Syndromes: It Is All in the Genes

REFERENCES 1. Hershman DL, Wilde ET, Wright JD, et al: Uptake and economic impact of first-cycle colony-stimulating factor use during adjuvant treatment of breast cancer. J Clin Oncol 30:806-812, 2012 2. Mukherjee S: The Emperor of All Maladies. New York, NY, Scribner, 2010, pp 423-429 3. Henderson IC, Berry DA, Demetri GD, et al: Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976-983, 2003 4. Giordano SH, Duan Z, Kuo Y-F, et al: Impact of a scientific presentation on community treatment patterns for primary breast cancer. J Natl Cancer Inst 98:382-388, 2006 5. Citron ML, Berry DA, Cirrincione C, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431-1439, 2003 6. Muss HB, Berry DA, Cirrincione C, et al: Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: The Cancer and Leukemia Group B Experience. J Clin Oncol 25:3699-3704, 2007 7. Piccart-Gebhart MJ: Mathematics and oncology: A match for life? J Clin Oncol 21:1425-1428, 2003 8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:1687-1717, 2005 9. Venturini M, Del Mastro L, Aitini E, et al: Dose-dense adjuvant chemotherapy in early breast cancer patients: Results from a randomized trial. J Natl Cancer Inst 97:1724-1733, 2005 10. Berry DA, Cirrincione C, Henderson IC, et al: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658-1667, 2006 11. Bonilla L, Ben-Aharon I, Vidal L, et al: Dose-dense chemotherapy in nonmetastatic breast cancer: A systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 102:1845-1854, 2010 12. Citron ML: Dose-dense chemotherapy: Principles, clinical results and future perspectives. Breast Care (Basel) 3:251-255, 2008 13. Hershman D, Neugut AI, Jacobson JS, et al: Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 99:196-205, 2007 14. Smith TJ, Hillner BE: Bending the cost curve in cancer care. N Engl J Med 364:2060-2065, 2011 15. Goldhirsch A, Wood WC, Coates AS, et al: Strategies for subtypes: Dealing with the diversity of breast cancer—Highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736-1747, 2011

Factorial design for randomized clinical trials

Factorial design for randomized clinical trials

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m− 2 day− 1 and i.v. 5-fluorouracil 1000 mg m− 2 day− 1, both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.

Patterns of care survey (PCS) in lung cancer: how well does current U.S. practice with chemotherapy in the non-metastatic setting follow the literature?

In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance status (PS) patients (pts). Pignon's meta-analysis [N Engl J Med 1992;327:1618-24] showed that combination chemotherapy (CT) and thoracic radiation (XRT) in LD-SCLC yielded an absolute 5.4% increase in 3-year survival versus chemotherapy alone. Concurrent chemoradiation upfront has generated the highest survival rates [Murray. J Clin Oncol 1993;11:336-44; Jeremic. J Clin Oncol 1996;15:893-900; Takada. J Clin Oncol 2002;20:3054-60]. In stage III NSCLC, multiple studies have shown therapeutic superiority for combination chemotherapy and XRT versus RT alone; and recent literature suggests a therapeutic advantage for concurrent chemoradiation versus chemotherapy followed by XRT [Curran. ASCO 2000;19:484a; Furuse. JCO 1999;17:2692-9; Zatloukal. ASCO 2002;A-1159]. Data are less secure regarding the role of chemotherapy in stage I and II NSCLC. A stratified two-step cluster sampling technique was used for data collection. Five hundred and forty-one individuals diagnosed between 1998 and 1999 with lung cancer, either LD-SCLC or stages I-III NSCLC were sampled from 58 institutions featuring radiotherapy facilities, giving a weighted sample size (wss) of 42,335 patients. All pts had Karnofski performance status (KPS) >or=60. We determined the percentage who received chemotherapy; the nature of chemotherapy and its timing with respect to XRT. SUDAAN statistical software was used to allow the incorporation of the design elements and weights to reflect the relative contribution of each institution and each patient in the analysis Of 72 (wss=6138) pts with LD-SCLC, 100% received XRT and 95% received chemotherapy (CT); 66% received concurrent (con) CT and XRT, of whom 29% also received CT pre XRT; 22% received CT post XRT as well, and 23% received both: 63% received sequential CT-->XRT+/-con CT; and 38% received some CT after XRT. Fifty-two percent received cisplatin (DDP), and 38% received carboplatin (CBDCA); 73% received etoposide (VP-16), while 10% received paclitaxel. Of 469 pts (wss=36,197) with NSCLC, 52% received CT, including 30% with stage I disease, 48% with stage II NSCLC, 60% with stage III NSCLC, and 50% with unknown stage. Thirty-nine percent received sequential CT-->XRT+/-CT, of whom 49% received CT pre XRT only. Seventy-four percent received con CT and XRT; and 27% received posterior CT, of whom 84% also received con CT/XRT. Forty-five received some CT in the pre-op setting and 15% in the post-op setting. Twelve percent received DDP-based therapy, while only 13% and 7% received VP-16 or vincas, respectively; 67% received CBDCA. Seventy-two percent received taxanes, of whom 96% received paclitaxel. Gemcitabine was administered to 3% of NSCLC pts. Combined modality therapy is typically employed in the therapy of LD-SCLC and LA-NSCLC. The majority of those treated for SCLC receive concurrent CT/XRT, while nearly 3/4 of those treated with CT and XRT for LA-NSCLC received concurrent CT/XRT. Current practice in the US generally matches evidence-based literature, although a significant percentage of practitioners substitute CBDCA for DDP in both venues and use paclitaxel in lieu of vincas or etoposide in NSCLC.

Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741

Using a 2 x 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (II) sequential A x 4 --> T x 4 --> C x 4 every 2 weeks with filgrastim, (III) concurrent AC x 4 --> T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim. A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P =.010), and OS (RR = 0.69; P =.013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

Continuous Course Radiation Therapy and Concurrent Combination Chemotherapy for Squamous Cell Head and Neck Cancer

Concurrent radiation therapy and chemotherapy is a promising approach to the treatment of squamous cell head and neck cancer. Toxicity, however, has required either scheduled breaks in radiation therapy administration or compromise in chemotherapy dose intensity. We describe the toxicity and results in 19 patients treated at diagnosis with a continuous course of radiation therapy and intensive concurrent combination chemotherapy using 5-fluorouracil and cisplatin. Toxicity among these 19 patients was significant, including mucositis, myelosuppression, and weight loss, and aggressive supportive efforts were required. No toxic deaths occurred, however. At the end of treatment, all patients had achieved complete control of their primary-site tumor. Primary-site resection was not required in any patient for tumor control, but neck dissections were performed in selected individuals with involved nodes at diagnosis. No patient recurred at the primary site and only a single patient recurred in the neck. We conclude that this chemoradiotherapy schedule is very effective, albeit toxic. Toxicity, however, can be managed with appropriate aggressive supportive measures. Confirmation of these encouraging treatment results will require performance of a randomized clinical trial.

Treatment of locally advanced non-small cell lung cancer

In this review the following topics are discussed: the complexities of clinical staging in locally advanced non-small cell lung cancer, the results of Phase III non-surgical combined modality studies, the results of Phase II neoadjuvant surgical trials. Although there have been conflicting results, most studies comparing survival of patients with clinical Stages IIIA and IIIB lung cancer have shown significant survival differences between these stage groups. It also appears that patients whose clinical stage is T3, N0 may have the best prognosis and may be the group most likely to benefit from combined-modality treatment. Additional staging data based on findings at mediastinoscopy are needed to confirm this initial observation. Sequential treatment with cisplatin-containing combination chemotherapy followed by radiation appears to produce a modest increase in 2-year survival rates. Further information regarding the effectiveness of this treatment sequence will be provided by a large, ongoing randomized trial comparing radiation alone versus two courses of vinblastine/cisplatin, followed by thoracic irradiation. In a recently reported study thoracic irradiation and concurrent daily cisplatin have produced significantly better survival than radiation alone or radiation combined with weekly cisplatin. Phase III trials of radiation and concurrent combination chemotherapy — particularly etoposide and platinum — should also be done. Both mitomycin/vinblastine/cisplatin and etoposide/cisplatin given with concurrent thoracic irradiation have produced relatively high response rates and encouraging survival results when given prior to pulmonary resection in patients with Stage IIIA non-small cell lung cancer. However, concern about toxicity has resulted in the deletion of mitomycin from an ongoing Phase III trial testing preoperative chemotherapy. In contrast, Phase II trials of preoperative etoposide/cisplatin plus radiation have produced relatively high response rates with acceptable toxicity. These observations have led the Southwest Oncology Group to propose the development of a Phase III trial testing this regimen as preoperative treatment.