As far as Avastin, NCCN supports second line use of Avastin alone or in combination – on p. OV-D, 1.

In terms of putting the two drugs together, only one recently completed study addresses this question. Fourty patients received a median of 8 treatment cycles. Toxicity was generally mild or moderate, and median Progression Free Survival and Overall Survival were 7.8 (95% confidence interval and 16.6 months , with 22 (55%) patients progression-free for ≥6 months. Patients treated with 2 prior regimens received greater benefit than patients treated with 1.

It concluded that a weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

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I found that 2011 ASCO educational book favors continuing Avastin into consecutive line of therapy but the only evidence that it adduced is from the BRITE study, which was for colon cancer and not ovarian cancer.

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At the 2010 American Society of Clinical Oncology Annual conference in Chicago, the Gynecologic Oncology Group(GOG) presented the results of the latest clinical trial for Avastin and ovarian cancer. GOG 218 (activated in October 2005) aims to randomly assign 2,000 patients in a three-arm placebo-controlled trial in which patients with stage III and IV disease receive paclitaxel and carboplatin, with or without bevacizumab (15 mg/kg every 21 days) for six courses, with a third arm continuing bevacizumab for an additional 48 weeks. Genentech, Inc., announced in February 2010 that the GOG Phase III study showed the combination of Avastin® (bevacizumab) and chemotherapy followed by maintenance use of Avastin alone increased the time women with previously untreated advanced ovarian cancer lived without the disease worsening (progression-free survival or PFS), compared to chemotherapy alone. Patients were randomly assigned to 3 treatment groups: paclitaxel 175 mg/m2 plus carboplatin area under curve (AUC) 6 cycles plus placebo maintenance; paclitaxel plus carboplatin and concurrent bevacizumab (15 mg/kg) and placebo maintenance; and paclitaxel plus carboplatin plus concurrent bevacizumab plus maintenance bevacizumab.Patients who received chemotherapy alone had a median progression-free survival of 10.3 months, compared with 11.2 months for those who received concurrent bevacizumab but placebo maintenance. GOG 218 study (Berger, ASCO 2009) only showed that, if the provider chooses to continue Avastin as maintenance, the result would be superior for the arm that included Avastin. It showed that Avastin maintenance is superior but did not answer the question of Avastin for the primary treatment itself. Women who received Avastin in combination with chemotherapy but did not continue maintenance use of Avastin did not have a longer progression free survival compared to those on chemotherapy alone. In other words, it showed that the two treatments are equivalent.

A recent  2010 abstract of ICON study presented at ESMO was also supportive. Women with high-risk early or advanced ovarian cancer gained almost two months in progression-free survival (PFS) when the angiogenesis inhibitor bevacizumab (Avastin) was added to chemotherapy, results of a large international clinical trial showed. Patients who received bevacizumab in addition to carboplatin-paclitaxel chemotherapy had a median PFS of 19 months, compared with 17.3 months for those treated with chemotherapy alone. Preliminary survival data from the 1,500-patient ICON7 study show a trend toward fewer deaths in the bevacizumab group, but survival data will not be mature for another two years. This ICON7 trial was a randomized trial. The control arm of the trial was standard chemotherapy with carboplatin and paclitaxel given in the usual way for 6 cycles, 1 cycle of treatment every 3 weeks, and then no further treatment. In the research arm of the trial, patients were treated with chemotherapy and bevacizumab for 6 cycles and then received bevacizumab for a further 12 cycles of treatment, which made 18 cycles or 12 months of treatment in total. The primary endpoint for our trial was progression-free survival and the study showed that progression was delayed and occurred less frequently in patients treated with bevacizumab than in patients in the control arm.

NCCN on p. MS-8 says that until the data is more mature, it does not recommend routine use of Avastin to first line chemotherapy or routine maintenance. Society of Gynecologic Oncology is more supportive but not definitive. It says: ” SGO encourages patients and providers to discuss risks, benefits and costs associated with use of bevacizumab as a component of upfront treatment and maintenance therapy.”

At this point, the presented data had been peer-reviewed and published. The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. It has not been incorporated into NCCN guidelines as of January of 2012 but seems destined to be.

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Two randomized prospective studies were  and a recent combination study with with metoclopramide, dexamethasone confirm octreotide effectiveness in MBO.

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Of more importance is the decreased number of false negatives or undetected cancers when OVA1 is added to a physician’s assessment This number is reduced from 28% to 8% in non-gynecologic oncologist assessment and from 21% to 1% in gynecologic oncologist assessment. This translates into potentially more cancers being referred to a gynecologic oncologist for initial surgery. The investigators go on to say, “Hopefully, earlier referral of patients with ovarian cancer will improve survival and reduce the number of required re-operation.” However, guidelines have not fully incorporated this test into their follow-up strategy or their assessment of recommendations on how to assess an ovarian mass. NCCN does not recommend or discuss this test.

ACOG/SGO Committee Opinion: Number 477 (March 2011) recommends that a woman with a suspicious or persistent complex ovarian mass requires surgical evaluation by a physician trained to appropriately stage and reduce the bulk of ovarian cancer. When referring to OVA1, the Committee states that OVA1 “appears to improve the predictability of ovarian cancer in women with pelvic masses. “A letter dated September 2009 issued by the Society of Gynecologic Oncologists recognized the importance of OVA1 stating that it “…may help healthcare providers better detect when referral to a gynecologic oncologist is indicated.”

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Trans Arterial Chemoembolization is often used for hepatocellular carcinoma and neuroendocrine cancers of the liver. However for other types of cancer, less information is available.  The safety and effectiveness of chemoembolization for breast cancer metastases is unknown as only case reports and series have so far been reported. The largest series reported in a 2008 abstract was of 217 patients but this was not a prospective study.

The Society of Interventional Radiology (SIR, 2009) stated that chemoembolization has shown promising early results with some types of metastatic tumors but that the evidence in the current medical literature is insufficient to demonstrate the efficacy of TACE for the treatment of liver metastases from other primary tumors, including but not limited to breast cancer, colorectal cancer, and other tumors of unknown primary sites, from ovarian cancer. Metastatic disease to the liver from tumors other than primary neuroendocrine tumors is generally treated with surgery, chemotherapy, or both.

Metastatic disease to the liver from ovarian cancer is somewhat less frequent than from breast cancer. A recent report from Vogl at al found that it is TACE is an effective palliative treatment in achieving local control in selected patients with liver metastases from ovarian cancer. It is the only study on this topic. This is similar to outcomes for the metastatic disease to the liver treated with TACE. Generally such results have not been thought to be adequate to recommend TACE of ovarian cancer because overall survival has not been increased.

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