Cancer Treatment Today » Chemotherapy

Mixed response

M Levin, MD — Sun, 14 Jul 2013 22:18:49 +0000

Traditionally, the field of oncology was interested in complete partial response and progression. Later stable disease came into use, a measure of chemotherapy success that combined tumor shrinkage and cases in which there had been no change. Any growth , usually greater than a 25% increase in tumor size was called progression. Mixed response refers to a situation in which some metastases are responding and others are growing and/or new metastases are appearing in the same time. It is a reflection of the fact that some cancer cells respond to therapy and others do not. A commonly used definition of types of mixed responses, when precision is required, such as in clinical studies, is that it is defined as >30% difference in individual lesion response, with all lesions showing a similar behavior; true mixed response (TMR) as two lesions showing progression versus response; homogeneous response (HR) is similar behavior of all lesions. Mixed responses are quite common in colorectal cancer; in one study of liver metastases, mixed responses were found in 30% of the patients. Unfortunately, this metric has been somewhat neglected and is not often included in clinical studies. As such, there had been little research and no guidelines to the oncologists on how to handle the mixed response situation. There appears to be a consensus that whether to change therapy depends on other available options, degree of security that the lesions that progressed truly progresses (as opposed to swelling or inflammation; some physicians advocate re-biopsy in unclear cases) and the number and size of non-responsive lesions.

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Chemotherapy causes acid reflux

M Levin, MD — Wed, 14 Nov 2012 17:03:41 +0000

Acid reflux is a not unknown side effect of chemotherapy. Chemotherapy aslo worsens symptoms in patients with pre-existing gastrointestinal reflux disorder(GERD), especially in esophageal cancer, where multiple local factors exacerbate it. Unfortunately, reflux had not been rigorously studied but a variety of medications are known to alleviate this side effect. Proton pump inhibitors(PPI) are useful in this condition. It stands to reason that therapy should be continued as long as chemotherapy continues and then stopped. PPI inhibitors are FDA indicated for short term use. This is based on concerns of indefinite symptomatic treatment preventing workup and diagnosis of potentially serious underlying conditions that cause reflux. Patients with cancer are not immune to other conditions causing GERD. The same considerations should lead to stopping PPI after chemotherapy is completed and, if GERD symptoms persist, a workup should be initiated.

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Tykerb for stomach cancer

M Levin, MD — Fri, 02 Nov 2012 12:24:51 +0000

Stomach cancer is known to have amplification of the ErbB2 (HER2) gene and responds to the drug Herceptin, which used this pathwayto attach cacner cells . Recently, there has been an interest in using Tyker(lapatinib) which is a drug that utalizes the same mechanism of action as Herceptin. One such trial is: LOGiC – Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib. This is an international multi-center trial for patients stomach, esophagus, or gastro-esophageal junction cancer with amplification of the ErbB2 (HER2) gene. The triallooks at whether lapatinib, when added to the chemotherapy regimen, capecitabine extends the time to progression and overall life. Chemothrapy is administered to all patients, who then randomly get either lapatinib or placebo. There is evidence of effectiveness for braa metastaes, at least in breast cancer(Lin et al).

Iqbal et al showed that Tykerb is an effective first line drug. The evidence thus far suggests that the combination of lapatinib + capecitabine shows promising efficacy and is well tolerated. The same appears to be true of Taxol and lapatinib and studies of this combination are ongoing.

A number of issues remain to study: how to combine Tykerb with toehr drugs, the role of Taykeb in patients previousely treated with Herceptin, and efficacyfor brain metastases.

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Incomplete response to induction in acute myelogenous leukemia and salvage approaches

M Levin, MD — Tue, 18 Sep 2012 20:56:42 +0000

Standard Therapy of acute myelogenous leukemia (excluding acute promyelocytic leukemia) begins with induction chemotherapy and is followed by consolidation and sometimes by maintenance phases of treatment. Various acceptable induction regimens are available. The most common approach is called ”3 and 7,” which consists of 3 days of a 15- to 30-minute infusion of an anthracycline (idarubicin or daunorubicin) or anthracenedione (mitoxantrone), combined with 100 mg/m2 of arabinosylcytosine (araC) as a 24-hour infusion daily for 7 days. Idarubicin is given at a dose of 12 mg/m2/d for 3 days, daunorubicin at 45-60 mg/m2/d for 3 days, or mitoxantrone at 12 mg/m2/d for 3 days. Using these regimens, approximately 50% of patients achieve remission with one course. Another 10-15% enter remission following a second course of therapy. Prognosis does not change based on whether one or two inductions were required to achieve a remission. A retrospective analysis of six Eastern Cooperative Oncology Group (ECOG) studies that included both younger and older adults demonstrated that 26% of patients achieving complete remission (CR) following anthracycline and cytarabine-based induction therapy required a second cycle of identical induction therapy to do so [Rowe et al. 2010].

Occasionally, a patient largely responds to two induction chemotherapies but is found to have persistent leukemia cells in the marrow. It is known that without farther intervention, such a patient is destined to relapse within a few months. Studies in 1980s and 1990s demonstrate that effective salvage regimens for relapsed or refractory AML include Ara-C and anthracycline-like compounds as the backbone of the regimens. Combinations that included flu-darabine and/or combinations of both Ara-C and anthracycline-like compounds also demonstrated efficacy and three drug salvage regimens are being studied. Also being explored are targeted agents, and allogeneic SCT, alone of in combinaitons. Prognostic significance of cytogenetic and other markers that can guide this choice is also being explored.

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Erbitux for squamous cell cancer of unknown primary site

M Levin, MD — Fri, 24 Aug 2012 17:18:34 +0000

About 5% of all metastatic cancers come from the primary in an organ that cannot be securely identified. This may make assigning therapy difficult. The histology of the location may or may not give sufficient clues to where the cancer rose. The usually recommended approach is to use various stains to try to pinpoint the area of origin and then treat for that type of cancer. However, this is not always possible.

When the primary site is not identified and when it does not fall neatly into certain specific clinical patterns, empiric front line broad-spectrum chemotherapy is recommended by NCCN. The issue remains second line chemotherapy. Erbitux is approved for second line treatment of squamous cell cancer of head and neck and is an attractive candidate for squamous unknown primary cancers. Unfortunately, these patients have a dismal prognosis despite management with a variety of chemotherapeutic combinations in small clinical studies. A recent meta-analysis showed no evidence of superior efficacy of any of the administered regimens incorporating platinum salts, taxanes or new generation cytotoxic compounds (gemcitabine, vinca alkaloids, irinotecan). Modest if any survival prolongation and symptom palliation with preservation of quality of life are the only realistic aims of therapy for these patients. Consequently, low-toxicity patient-convenient chemotherapy regimens should be administered to reasonably fit poor-risk patients. Currently neither ESMO nor NCCN recommend Erbitux even in first line. NCCN recommendations do not include Erbitux(OCC-B, 1) and neither guideline recommends second line chemotherapy.

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Rituxan and Rituxan with Gemcitabine for Hodgkin’s Disease

M Levin, MD — Thu, 09 Aug 2012 17:56:42 +0000

Until recently rituximab, or Rituxan has been thought of as a drug for Non-Hodgkin’s lymphoma. Rituxan® is a monoclonal antibody approved for treatment of non-Hodgkin’s lymphoma (NHL) and binds to a lymphoma surface molecule called CD 20. A small subset of patients with Hodgkin’s lymphoma (3% to 8%) has a type of cancer called CD 20 lymphocyte predominant Hodgkin’s lymphoma, characterized by a large proportion of their cancer cells expressing CD 20. Patients with CD 20 lymphocyte predominant Hodgkin’s lymphoma tend to have a higher rate of recurrence following standard therapy against Hodgkin’s lymphoma than other patients with Hodgkin’s lymphoma. According to results recently published in the journal Blood, Rituxan® (rituximab) appears to be a promising agent in the treatment of some patients with recurrent Hodgkin’s.

NCCN on p. HODG-E says that Rituxan should be considered for all patients with relapsed Hodgkin’s disease. It recommends it with ABVD for Lymphocyte Predominant Hodgkin’s in first line. It does not address other combination chemotherapy with Rituxan.

Gemcitabine has been combined with Rituxin and with rituximab and other drugs in studies for relapsed Hodgkin’s. These two drugs together in several phase II studies appear to be “mildly” active and well tolerated.

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Non-gonadal Germinomas

M Levin, MD — Mon, 06 Aug 2012 15:17:34 +0000

Germinoma is primarily a disease of young males. There are germinomas that arise in the testicles or ovaries, the gonads, and those that do not. It is presumed that the non-testicular germinoma have their origin in germ cells left behind in various places in the body during the development of the fetus. The current World Health Organization classification of Germ Cell Tumors (GCT), which is based primarily on histological elements, divides these tumors into the following major forms: Germinoma – Pure and with syncytiotrophoblasts, constituting 65%, NGGCT(non-gonadal, meaning non-testicular or ovarian)s, Teratoma – Mature and malignant, Embryonal carcinoma, Yolk sac , choriocarcinoma, endodermal sinus tumor and mixed, which combines these different elements.

Surgery and radiation are mainstays of treatment. More recently, chemotherapy has been added to the treatment regimens in order to permit the use of a lower radiation dose, thereby reducing the long-term morbidity associated with radiation therapy while maintaining the excellent survival rates. In patients with NG (non-gonadal) GCTs, the use of adjuvant chemotherapy with radiation therapy is intended to improve outcome, because even with surgery and CSI these patients have a poor prognosis. For NGCGT, chemotherapy prolongs survival. As with gonadal germ cell tumors, the agents that have best activity against CNS GCTs are cisplatin, etoposide, vinblastine, bleomycin, and carboplatin. No, but I guess lusted Ifosfamide and cyclophosphamide are also effective. High-dose chemotherapy followed by autologous stem cell transplant may be effective for patients who relapse.

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Second line chemotherapy for endometrial cancer

M Levin, MD — Wed, 20 Jun 2012 18:31:55 +0000

There is not much information on what to do after failure of first line chemotherapy in endometrial cancer. Currently, the standard of care for initial treatment of women who present with locally advanced disease or metastatic disease is anthracycline, taxane, and platinum combination. This is based on the Gynecologic Oncology Group (GOG) trial 177, which established the effectiveness of first-line paclitaxel, doxorubicin, and cisplatin (TAP) compared with doxorubicin and cisplatin (AP) in this population.

Ixabepilone has modest activity of limited duration as a second-line treatment in endometrial adenocarcinoma in those who largely received prior taxane therapy. In a recent phase II study, however, the activity of ixabepilone did not meet the pre-established threshold to move it forward in the GOG in this population.

In general, topotecan, ifosfamide, liposomal doxorubicin, and progestational agents have been generally used, although without strong literature-based support. Whether addition of Avastin to various combinations might change this situation is being investigated but second line chemotherapy for endometrial cancer at this time cannot be considered supported by medical literature.

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