Sequential therapy

In HBeAg-negative patients, 12 weeks of lamivudine monotherapy followed by 36 months of pegylated lFN-a2b therapy (including 3 months of concomitant administration) has been compared with 48 weeks of lamivudine monotherapy (Vassiliadis et al. 2007). At the end of follow-up, the rate of ALT normalization was significantly higher with the sequential therapy than with lamivudine alone. No difference in the proportion of patients with undetectable HBV DNA was observed. Similar results were obtained in a Chinese cohort study (Shi et al. 2006). 

The antiviral efficacy of IFN-p administered for 24 weeks at a dose of 3 million units daily has been studied in a small series of HBeAg-positive patients. HBe seroconversion was observed in half the patients and ALT normalization in four patients out of five (Kagawa et al. 1993). Sequential therapy with lamivudine and IFN-p has been tested in HBeAg-positive patients (Enomoto et al. 2007). A sustained virological response was achieved in only 7 (29%) of the 24 patients, 24 weeks after the end of therapy. In a pilot study of IFN-p therapy in 29 patients in whom IFN-a therapy had failed, HBV DNA became undetectable in 6 patients (21%) (Munoz et al. 2002). 

Enomoto M, Tamori A, Kohmoto MT, Hayashi T, Jomura H, Habu D, Sakaguchi H, Takeda T, Kawada N, Seki S, Shiomi S, Koh N, Nishiguchi S (2007) Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection. J Interferon Cytokine Res 27 201-207... 

Sarin SK, Kumar M, Kumar R, Kazim SN, Guptan RC, Sakhuja P, Sharma BC (2005) Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients. Am J Gastroenterol 100 2463-2471... 

The combination of a bisphosphonate with anabolic therapy (teriparatide) should not be used because a well-controlled trial showed that women receiving the combination actually had smaller increases in bone mineral density than women receiving teriparatide alone.44 However, sequential therapy with these agents may be more promising. In one study, women who received alendronate for 1 year directly after receiving parathyroid hormone for 1 year had greater... 

Discontinuation of therapy results in a decrease in BMD, but some antifracture efficacy appears to be maintained. Sequential therapy with teriparatide followed by an antiresorptive agent (e.g., bisphosphonate) should be considered to maintain BMD gains. 

Sequential therapy involves rapid clearing of psoriasis with aggressive therapy (e.g., cyclosporine), followed by a transitional period in which a safer drug such as acitretin is started at maximal dosing. Subsequently, a maintenance period using acitretin in lower doses or in combination with UVB or PUVA can be continued. 

The majority of patients can be managed with oral antimicrobial agents, such as trimethoprim-sulfamethoxazole or the fluoroquinolones (ciprofloxacin, levofloxacin). When IV treatment is necessary, IV to oral sequential therapy with trimethoprim-sulfamethoxazole or a fluoroquinolone, such as ciprofloxacin or ofloxacin, would be appropriate. 

Sequential therapy (IV to oral) may be instituted at the discretion of the physician. 

A Japanese trial compared sequential delivery of chemotherapy and radiation therapy to concurrent delivery of chemotherapy and radiation (47). Patients were randomized to receive concurrent hyperfractionated radiation therapy (d 2 of cycle 1 of chemotherapy) or to sequential chemotherapy followed after the fourth cycle by hyperfractionated radiation therapy. The radiation dose was45 Gygivenin 1.5 Gy fractions twice daily for a total of 30 fractions in 3 wk. The chemotherapy given was cisplatin and etoposide. The median survival for the concurrent schedule was 29 mo and for the sequential schedule was 19 mo. The 2-yr survival was 50% for the concurrent therapy and 40% for the sequential therapy (47). These results favored concurrent therapy and are the best results to date for patients with LD-SCLC. 

Sequential Therapies Locally Advanced Breast Cancer ... 

LOCALLY ADVANCED BREAST CANCER SEQUENTIAL THERAPIES... 

Jafri NS et al Meta-analysis Sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med 2008 148 923. [PMID 18490667]... 

However, in 12 patients who took letrozole 2.5 mg/day for 6 weeks with and without tamoxifen 20 mg/day plasma concentrations of letrozole were reduced by 38% during combination therapy (39). Tamoxifen did not significantly alter the effect of letrozole in suppressing estradiol, estrone, and estrone sulfate. The authors suggested that sequential therapy might be preferable with these two drugs. 

Combination chemotherapy administered concurrent with radiation has produced the most promising results in advanced, unresectable disease. The important study of Merlano et al. randomized 157 patients to conventional radiotherapy vs. cisplatin/5-FU given concurrent with radiation in alternating weekly fashion. They reported a 3-year survival rate of 41% with concurrent therapy vs. 23% with radiation alone (p < 0.05) and 5-year survival rate of 24% vs. 10% (p < 0.02) [136]. Taylor et al. reported significantly improved disease-free survival rates in patients treated with concomitant cis-platin/5-FU and radiation over sequential therapy (17 months vs. 13 months, p = 0.003) in their study of 214 patients with unresectable disease [137]. 

Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004 350 971-1046. 

Combination, rotational, and sequential therapy is commonly used in treatment of psoriasis to achieve a response, increase effectiveness of treatment, or enable lowering of doses of individual agents. 

Koo J. Systemic sequential therapy of psoriasis a new paradigm for improved therapeutic results. J Am Acad Dermatol 1999 41 S25-S28. 

Noguchi, S., Yamamoto, H., Inaji, H., Imaoka, S., and Koyama, H., Influence of tamoxifen-medroxyprogesterone sequential therapy on estrogen and progesterone receptor contents of breast cancer. Jpn. J. Cancer Res. 80(3), 244-248 (1989). 

Sequential therapy involving clobetasol proprionate cream 0.05% for 8 weeks followed by azelaic acid cream 20% for 16 weeks revealed excellent clearance of melasma compared to azelaic acid 20% monotherapy. Better results are also obtained if a glycolic acid cream is applied sequentially to azelaic acid treatment. 

Sarkar R, BhaUa M, Kanwar AJ (2002) A comparative study of 20% azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark-skinned patients. Dermatology 205 249-254... 

Chemoembolization Moertel et al. (1994) have chronicled their 10 year experience in 111 patients with neuroendocrine hepatic metastases, usually hypervascular, receiving vascular occlusion therapy by a variety of methods. A total of 71 patients also received subsequent alternating chemotherapy regimens (dacarbazine + doxorubicin and streptozotocin + 5-fluorouracil). Objective regression rates of 60% with vascular occlusion alone and 80% with sequential therapy of vascular occlusion and chemotherapy were observed. A median survival time of 37 months was experienced in patients with islet cell carcinoma and 49 months with carcinoid hepatic metastases. Repeated embolizations were preferred. 

Infection risk Fatal disseminated systemic nocardiosis with Nocardia farcinica, involving the brain, lymph nodes, and adrenal glands, occurred in a 66-year-old woman with psoriasis after sequential therapy with alefacept and then infliximab [92 ]. 

Pei R, Cao J, Ma J, Zhang P, Liu X, Du X, et al. Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. Hematology 2012 17(6) 311-6. 

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