Cancer Treatment Today » New Drugs

Olysio and Sovaldi: Two new drugs for Hepatitis C

M Levin, MD — Fri, 03 Jan 2014 14:24:52 +0000

Hepatitis C is a major public health problem, especially in Southeast Asia. Interferon and ribavirin have been the standard of care in various combinations. The literature supports intereferon with the two recently FDA approved oral medications that can be used in combination with the current antiviral regimen or to replace the injectable component of the regimen, peginterferon alfa.

The two new drugs are Olysio (simeprevir) capsules and Sovaldi (sofosbuvir) tablets. Both work by stopping the replication of the Hepatitis C virus.

Olysio 150 mg capsules are a once-daily treatment that must be used in combination with pegylated interferon (peginterferon alfas like Pegasys or Pegintron) and ribavirin. It cannot currently be used as monotherapy, which means it can’t be used alone. Sovaldi 400 mg tablets are a once-daily treatment that can be used without the injectable peginterferon alfa. This is novel and helpful in hepatitis therapy because the peginterferon alfa injectable often contributes to patients not finishing their course of Hep C therapy due to the unfavorable side effects.

Based on a side-by-side review if disparate studies, Sovald appears to be more versatile than Olysio as it is approved for treatment of genotypes 1, 2, 3 and 4. Also, for genotype 2 and 3, Sovaldi can be taken with ribavirin alone, excluding the need for interferon altogether. (Interferon, perhaps the most dreaded component of HCV therapy, is administered by injection and many side effects. On the other hand, Olysio must always be used in combination with interferon and ribavirin for the duration of either 24 weeks (for treatment-naive patients) or 48 weeks (for patients previously exposed to HCV therapy). However ,it cannot be used with many retroviral drugs.

Using the two together is beginning to be explored, with early results showing efficacy in even hard-to-treat cases. In early January, the New England Journal published a study of the combination of these two drugs. he New England Journal of Medicine, investigators designed a Phase II open-label study of Gilead Sciences’ recently approved nucleotide analogue NS5B polymerase inhibitor Sovaldi and Bristol-Myers Squibb’s NS5A replication complex inhibitor daclatasvir.

Sulkowski MS, et al “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection” N Engl J Med 2014; 370: 211-221.

Sovaldi, Prescribing Information 2014

Ferriprox for sickle cell anemia

M Levin, MD — Wed, 17 Jul 2013 18:30:31 +0000

FERRIPROX® (deferiprone) is an iron chelator indicated for the treatment of patients with iron overload form transfusions due to thalassemia syndromes when current chelation therapy, most commonly Exjade, is inadequate. The approval in second line is reasonable both because the studies for approval were done in second line and because Ferroprox may be inferior to Exjade in first line (Cemak et al). This is not an innocuous drug; the most serious side effect seen in about two percent of patients treated with Ferriprox was the development of bone marrow failure to produce white cells, a serious and potentially life-threatening complications. The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients, or on an effect on a clinical endpoint other than survival or irreversible morbidity (illness).

ApoPharma has agreed to several post-marketing requirement and commitments. One commitment includes further study of the use of Ferriprox in patients with sickle cell disease who have transfusional iron overload. One such study is: Absorption, Metabolism, and Excretion of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease, NCT01835496.

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Zolinza for maintenance in glioblastoma

M Levin, MD — Mon, 13 May 2013 12:40:37 +0000

With the advent of biologic therapies, many new avenues to approach recalcitrant and difficult diseases have emerged. Once such cancer is the brain cancer glioblastoma(GBM). It is tempting to use Zolinza(vorinostate) for maintenance after attaining a remission of glioblastoma, because this is a disease that almost always comes back.

Unfortunately, there is as of yet no literature supporting the use of Zolnza for maintenance for gliolastoma. A recent study for recurrent disease by Galanis et al concluded that vorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling, sophisticated wyas to look at what this drug is doing to the cancer cells, indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.

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Zolinza for Hodgkin’s

M Levin, MD — Fri, 01 Mar 2013 21:03:38 +0000

Current chemotherapy drugs are very effective for Hodgkin’s lymphomas but patients who relapse after receiving them don;t do as well. This is because the cancers develop resistance to the se drugs. Zolinza is a new drug approved in the USA for the treatment of cutaneous(skin) T-cell lymphoma who have progressive, persistent or recurrent disease or following two systemic therapies. It may be effective for Hodgkin’s. For Hodgkin’s, a phase II study enrolled twenty-five eligible patients. The overall resposne rate was low, 4% (one partial response), but the drug was well tolerated. A phase I clinical trial treated several types of lymphoma. The best responses were seen in those with Hodgkin and diffuse large B-cell lymphoma (Budde et al). A study of Vorinostat and Lenalidomide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma was started at the City of Hope but was terminated.

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Megace and Megace ES

M Levin, MD — Sun, 24 Feb 2013 05:19:38 +0000

Megace has long been shown to help weight gain in cancer and AIDS. More recently, Megace ES came on the market. The advantage is in the concentrated dose that Megace ES offers. It is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

The recommended adult initial dosage of Megace ES (megestrol acetate) oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). The equivalent Megace dose it 800 mg and requires 20 ml. These drugs are are bioequivalent in a fed state.
However, in unfed patients Megace ES achieved 5 times greater peak plasma levels than Megace suspension. Additionally, the study demonstrated that a lower volume of Megace ES achieved maximum blood concentration more rapidly than the currently available oral suspension products.

However, the two products were not directly compared in regard to clinical effectiveness and it is not known if this pharmacokinetic advantages translate into any clinical advantage.

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Zelboraf for other mutations that BRAF-E

M Levin, MD — Fri, 08 Feb 2013 15:49:48 +0000

Zelboraf(vemurafenib) is anti BRAF kinase inhibitor. ZELBORAF™ is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test.

More than 30 mutations of the BRAF gene associated with human cancers have been identified. However, most of them work thorugh pathways and in a similar way to the BRAF-E. With this in mind, other BRAF mutations than E should also respond to Zelboraf. In the Chapman study, on which the FDA approval was based, there were ten patients with BRAF-K mutation and they showed some response. Ten patients in the vemurafenib group were later found to have BRAF V600K mutations; of these patients, 4 had a partial response (40%). Being that there are so many different BRAF mutations, it is not reasonable to require large studies performed for each mutation subtype.

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Rituxan and vasculitis

M Levin, MD — Sun, 20 Jan 2013 22:05:26 +0000

The U.S. Food and Drug Administration in April 2011approved Rituxan (rituximab), in combination with glucocorticoids (steroids), to treat patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA), two rare disorders that cause blood vessel inflammation (vasculitis). Case reports and sereis suggest that it may also be effective in otehr types of vasculitis, particularly those with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Several patients with chronic cutaneous small-vessel vasculitis have also been treated effectively with this agent. Interestingly, one case report suggested that Rituxan itself can cause leukocytoclastic vasculitis.

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Sprycel after failing Gleevec

M Levin, MD — Thu, 17 Jan 2013 17:01:41 +0000

On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) with resistance or intolerance to prior therapy including imatinib. The approval was based on four single-arm multicenter studies that combined 445 patietns and supported the efficacy and safety of dasatinib.

The FDA approval was for newly diagnosed patinets; however, there is evidence that Sprycel is effective in patients who fail imatinib as well. Study CALGB 180-034 was designed to assess the efficacy and safety of dasatinib following intolerance or resistance to imatinib. With six years fo followup, thirty-one percent of patients randomised to receive dasatinib 100 mg once daily remained on treatment. There was progression-free survival of 49.3% and an overall survival of 71% for with 6% of patients (n=10) progressing to accelerated or blast phase on study at six years of follow-up. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention.

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Stivarga for GIST tumors

M Levin, MD — Fri, 28 Dec 2012 11:33:53 +0000

GIST(Gastrointenstinal Stromal Tumor) is the most common form of sarcoma in the gastrointestinal tract. There are thought to be 4,000-5,000 new cases of GIST diagnosed each year in the USA, about 1,500 of them metastatic. Two treatments for GIST has been recently FDA approved. Recently, FDA also approved regorefanib, Stivarga, for colon cancer, based on the CORRECT trial. The application for approval is for GIST is now pending before the FDA. It is based on the recent GRIP study of 132 third line patientswho either received regorafenib 160 mg once daily or placebo. There was no overall survival difference, possibly related to the crossover design of the study (85% crossed over to regorefanib). Progression-free survival, however, another indicator of effectiveness, was almost five times greater in the regorafenib group at 4.8 months compared with 0.9 months in the placebo group. The disease control rate was also significantly greater – 52.6% compared with 9.1% for placebo-treated patients.

Efficacy is also supported by a phase II trial published in 2012 by S. George et al. Bayer has began to offer regorefenib to patients with GIST on a compassionate use basis.

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Melanoma: Retreating with Yervoy

M Levin, MD — Sun, 23 Dec 2012 19:57:23 +0000

Yervoy is recently approved drug that induces an ummune response against melanoma cells. )Some patients have only a partial response or progress afer responding, and owing to there not being many other good options, many doctors would retreat in such a situation. However, Yervoy is a toxic drug and the decision to use it again is not a trivial one. It is , unfortunately, not known whether retreatment is beneficial. There is a study looking at this question: Study to Compare the Effect of Ipilimumab Retreatment With Chemotherapy in Advanced Melanoma, NCT01709162. The purpose of the study is to determine whether additional doses of Ipilimumab have a positive effect on survival in the treatment of advanced melanoma that has progressed after successful initial treatment with Ipilimumab. In the meantime, NCCN supports retratment providing that there had been a response after first use and no toxicity and that 3 months have passed.

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