Two large randomized controlled clinical trials sponsored by the National Cancer Institute involving more than 3300 patients with early-stage HER-2 positive invasive breast cancer found that those patients who received trastuzumab in combination with standard chemotherapy (doxorubicin and cyclophosphamide followed by paclitaxel) had a statistically significant 52% decrease in risk for breast cancer recurrence compared with patients who received chemotherapy alone 2. These studies included women with HER2 positive and node positive breast cancer with no distant metastatic disease. One study also included persons with high risk node negative breast cancer: tumor greater than 2 cm, estrogen/progestin receptor negative, nuclear grade 2-3 or age less than 35 years. In one study, Herceptin therapy was administered weekly for three months, then every 21 days for one year. In another study, This is the regimen used in this case.
Herceptin therapy was administered weekly for one year. Four years into the study, 85 percent of women with early-stage HER-2 positive breast cancer who received trastuzumab were free of recurrence, compared with 67 percent of women who did not receive the drug. The data monitoring committees overseeing the combined analysis of these trials recommended that the results of a combined interim analysis be made public because the studies had met their primary endpoints of increasing disease-free survival and overall survival in patients receiving trastuzumab in combination with chemotherapy. Most patients in these studies had lymph node-positive breast cancer, with only a minority having lymph node-negative disease. The limited information in the node-negative group did not allow for a separate analysis of this group. In these studies, the likelihood of congestive heart failure in women receiving standard combination chemotherapy and trastuzumab was increased by 3 percent to 4 percent. However, subsequent studies were more supportive 5.

An international, multicenter, randomized controlled clinical trial (Herceptin Adjuvant Trial (HERA)) found that one year treatment with trastuzumab after adjuvant chemotherapy significantly improved disease free survival among women with early stage HER-2 positive breast cancer 1. The study compared one or two years of trastuzumab given every three weeks with observation in women with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy (surgery with or without radiotherapy) and at least four cycles of neoadjuvant or adjuvant chemotherapy. Eligible subjects had node positive disease (regardless of tumor size) or node-negative disease (if tumor size was greater than 1 cm) and no distant metastases. Subjects in the HERA study were assigned to three groups: two years of treatment with trastuzumab, one year of trastuzumab, and observation. The study by Piccart-Gebhart reported results only of the groups assigned to one year of trastuzumab treatment and observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second non-breast malignant disease, or death) were observed; 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval 0.43 to 0.67), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percent. Overall survival in the two groups was not statistically significantly different (29 deaths with trastuzumab versus 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.

In conclusion, both NCCN and NICE support this regimen for adjuvant use in early breast cancer.

1.National Comprehensive Cancer Network (NCCN). Breast cancer. Clinical Practice Guidelines in Oncology — v2.2005. Jenkintown, PA: NCCN; 2015.
2.Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
3.Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.
4.Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005;353(16):1734-1736.
5.NICE clinical guideline 80 (Breast cancer: early and locally advanced, published in February 2009)

The impact of maintenance treatment with rituximab on overall survival is one of the most important open questions for patients with indolent non-Hodgkin lymphoma. Recent randomized trials performed by the German Low Grade Lymphoma Study Group (GLSG) and by the EORTC demonstrated the superiority of rituximab maintenance after immunochemotherapy and after chemotherapy compared with observation alone.

Clinical trials have demonstrated prolongation of progression-free survival and, in some cases, increased survival when “maintenance” rituximab is given following rituximab induction, chemotherapy induction, or rituximab/chemotherapy (relapsed setting).

A recent guideline says this about maintenance rituximab for low grade lymphoma: “For previously treated patients with follicular or other indolent B-cell-histology lymphoma (such as mantle cell lymphoma, marginal zone lymphoma, and lymphoplasmacytoid lymphoma), excluding small lymphocytic lymphoma (SLL):
However, a Canadian guideline does recommend this approach and it is becoming the predominant approach in clinical practice.NCCN also lists it as category 1 recommendation on p. FOLL-B. First line extended therapy – If initially treated with single-agent Rituxan, consolidation with Rituximab 375mg/m2 one dose q 12 weeks is supported. FDA approved Rituxan as a maintenance therapy for patients with advanced follicular lymphoma in January of 2011. Farthermore, NCCN marginal lymphoma guideliens take one to the follicular lymphoma pages, where maintenance is recommended

On June 13, 2011, at the 16th Congress of the European Hematology Association in London, there was presented a study of maintenance rituximab after responding to initial therapy. It was restricted to elderly patients and showed that maintenance doubled the duration of remission doubled. Overall survival at 4 years also improved with rituximab maintenance, and experts suggest it should become the new standard of care. At 4 years, 57% of the patients treated with rituximab were still in in remission, compared with 26% of those treated with interferon (P = .0117). ” This study has not yet been published. The schedule is not NCCN prescribed and various schedules have been reported. NCCN recommends up to 2 years of maintenance therapy on FOll-B, 1

For large cell lymphoma, NCCN does NOT recommend maintenance Rituxan. Rituxan after CHOP, but not after R-CHOP, significantly prolongs TTF, but fails to prolong OS, possibly due to a delayed pattern of relapse and/or the efficacy of rituximab in the salvage setting(An Intergroup E4494/C9793 update). NCCN on p. BCEL specifically states that and does not recommend it.

For mantle cell lymphoma, NCCN also does not recommend maintenance. On June 13, 2011, at the 16th Congress of the European Hematology Association in London, there was presented a study of maintenance rituximab after responding to initial therapy. It was restricted to elderly patients and showed that maintenance doubled the duration of remission doubled. Overall survival at 4 years also improved with rituximab maintenance, and experts suggest it should become the new standard of care. At 4 years, 57% of the patients treated with rituximab were still in in remission, compared with 26% of those treated with interferon (P = .0117). ” This study has not yet been published.

NCCN recommends it for marginal zone lymphoma

NCCN, MZA-A, 2 2017

NCCN.ORG, NHLm follicular 2017

NCCN, MANT-4 2017

Revised 2/4/2012

Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]

S. J. Horning
Optimizing Rituximab in B-Cell Lymphoma
J. Clin. Oncol., February 20, 2005; 23(6): 1056 – 1058.

John D. Hainsworth, Sharlene Litchy, Don W. Shaffer, Van L. Lackey, Manuel Grimaldi, F. Anthony Greco, Maximizing Therapeutic Benefit of Rituximab: Maintenance Therapy Versus Re-Treatment at Progression in Patients With Indolent Non-Hodgkin’s Lymphoma—A Randomized Phase II Trial of the Minnie Pearl Cancer Research Network
Journal of Clinical Oncology, Vol 23, No 6 (February 20), 2005: pp. 1088-1095

Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006;24:3121–3127.

NCCN lists options for metastatic disease in a carefully worded way (without addressing specific protocols), with recommendations for oxaliplatin, cisplatin, 5FU, taxane or irinotecan (Camptosar) based therapy.

We eagerly await the results of the many cooperative group and single-institution clinical trials exploring the role of cetuximab in esophageal cancer. These include a South-west Oncology Group (SWOG) trial of cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma, a Memorial Sloan-Kettering Cancer Center study of cetuximab in irinotecan/cisplatin-refractory patients with metastatic esophageal cancer and a Dana-Farber Cancer Institute preoperative trial with cisplatin, irinotecan, cetuximab, and radiation in locally advanced esophageal cancer. In two phase I studies, EGFR-directed antibodies have shown activity in patients with esophageal cancer. In the phase I study of the humanized EGFR mAb EMD72000, one patient with metastatic, pretreated squamous cell carcinoma had a durable, 6-month PR. In addition, a phase I trial with ABX-EGF, a high-affinity, fully human IgG2 EGFR mAb, reported stable disease for 7 months in one esophageal cancer patient. Two recent studies presented at the 2006 meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) suggest that Erbitux® (cetuximab) can be safely added to combination chemotherapy regimens for rectal and esophageal cancer. However, these are studies with radiation and in early phase II. At ASCO 2011, a French group rpesented a study of Folfox with Erbitux. The treatment was two cycles of FOLFOX induction therapy plus cetuximab, followed by radiotherapy at 50.4 Gy with FOLFOX. Cetuximab, 250 mg/m², was given weekly during induction and during the three cycles of chemoradiotherapy.

Results are summarized in the table. NCCN(ESOPH-E,3) lists various irinotecan. taxane platin combinations and does list Erbitux for second line to be combined with other regimens. This is level 2B recommendation.

(The Cochrane Database of Systematic Reviews 2006 Issue 4 Chemotherapy for metastatic (spread to other parts of the body) cancer which originates in the esophagus.

Malthaner R, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database Syst Rev 2003;(4):CD001556.

NCCN.ORG, Esophageal Cancer

Tew, William P. , Kelsen, David P. , Ilson, David H.
Targeted Therapies for Esophageal Cancer
Oncologist 2005 10: 590-601;

Roedel C, Arnold D, Hipp M, et al. Cetuximab in combination with capecitabine, oxaliplatin and concomitant radiotherapy (Cet-Capox-RT) as preoperative therapy for rectal cancer. International Journal of Radiation Oncology* Biology*Physics. 2006;66, issue 3, Supplement:S82-S83, abstract 147.

Suntharalingam M, Dipretrillo T, Wanebo H, et al. A phase II trial evaluating the efficacy of weekly cetuximab, paclitaxel, carboplatin and daily RT in esophageal cancer. International Journal of Radiation Oncology* Biology*Physics. 2006;66, issue 3, Supplement:S22-S23, abstract 40.

Lledo G, Michel P, Dahan L, et al: Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX). 2011 Gastrointestinal Cancers Symposium. Abstract 8. Presented by Aimery de Gramont, MD, January 20, 2011.Figlin RA, Belldegrun AS, Crawford J et al. ABX-EGF, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with advanced cancer: phase 1 clinical results. Proc Am Soc Clin Oncol 2002;21:10a.

William P. Tew, David P. Kelsen, David H. Ilson Targeted Therapies for Esophageal Cancer The Oncologist, Vol. 10, No. 8, 590-601, September 2005;

J. Tabernero*, T. Macarulla, F. J. Ramos and J. Baselga Novel targeted therapies in the treatment of gastric and esophageal cancer Annals of Oncology 2005 16(11):1740-1748;

Revised: 8/2/2011

On February 12, 2004, the FDA approved cetuximab (Erbitux) under its accelerated approval program as a combination treatment with irinotecan for the treatment of patients with metastatic colorectal cancer; or alone if patients cannot tolerate irinotecan. The approval of cetuximab by the FDA was largely based on the findings of a randomized, controlled study with 329 patients – 218 for cetuximab plus irinotecan combination therapy and 111 for cetuximab monotherapy. Furthermore, cetuximab was examined as a single agent in a third clinical study with 57 patients. Safety data from the 111 patients treated only with cetuximab was also assessed. All of the studies included patients with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving irinotecan. Results of these trials showed that the combination treatment of cetuximab and irinotecan shrank tumors in 22.9 % of patients and delayed tumor growth by 4.1 months. For patients who received cetuximab alone, the tumor response rate was 10.8 % and tumor growth was delayed by 1.5 months. However, it should be noted that although cetuximab has been reported to shrink tumors in some patients and delay tumor growth, especially when used as a combination treatment, it has not been shown to increase survival.Thierefore, irinotecan and Erbitux and standard for second line therapy or later lines of therapy for colon cancer, as per guideline recommendations, such as NCCN.

Recently MSKCC researchers reported a combination of cetuximab and Avastin.This trial included 83 patients with advanced colorectal cancer who did not respond to treatment with Camptosar alone. No patients had received prior therapy with Erbitux or Avastin. One group of patients was treated with Erbitux/Avastin/Camptosar, and the other group was treated with Erbitux and Avastin.

• Time to cancer progression was 7.3 months for patients treated with Erbitux/Avastin/Camptosar versus 4.9 months for those treated with Erbitux/Avastin.
• Anticancer responses were achieved in 37% of patients treated with Erbitux/Avastin/Camptosar versus 20% for those treated with Erbitux/Avastin.
• Overall survival was 14.5 months for patients treated with Erbitux/Avastin/Camptosar compared with 11.4 months for those treated with Erbitux/Avastin.

The researchers concluded that, when compared to historical data including Erbitux alone, the addition of Avastin to Erbitux plus Camptosar or to Erbitux alone appears to enhance effectiveness in the treatment of advanced colorectal cancer among patients who do not respond to Camptosar. As well, the addition of Camptosar to Avastin and Erbitux appears to provide improved anticancer activity over that of Avastin and Erbitux alone.

Cohen RB. Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clin Colorectal Cancer. 2003;2(4):246-251.

O’Neil BH, Goldberg RM. Novel chemotherapeutic and targeted agents in metastatic colorectal cancer: The time has arrived. Expert Opin Investig Drugs. 2003;12(12):1939-1949.
Saltz L, Lenz H-J, Kindler H, et al. Randomized Phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: The BOND-2 Study. Journal of Clinical Oncology. 2007;25:4557-4561.

Revlimid is an orally administered derivative of thalidomide, which is a very active agent for the treatment of multiple myeloma but has serious side effects, especially thromboembolism. Revlimid is reported to have less toxicity than thalidomide but retains antimyeloma effects. Revlimid has recently been approved by the FDA for review of treatment of myelodysplastic syndromes (MDS) wih a 5q- mutation and for first line treatment of multiple myeloma in conjunction with dexamethasone. Revlimid is in clinical trials for the evaluation of treatment for other hematologic cancers including CLL.

There are many studies supporting effectiveness of Revlimid, although most of them are small and presented in the abstract form.

Researchers from the Roswell Park Cancer Center and the Toronto Sunnybrook Regional Cancer Center have reported that Revlimid has significant activity in CLL. This study was also presented at the 2005 meeting of the American Society of Hematology in December 2005. Thalidomide has also demonstrated activity when combined with Fludara for initial treatment of CLL. This was a small study involving only 16 patients, but the complete response rate was over 50%.

The study presented at ASH 2005 and ASCO 2006 involved 29 patients with relapsed or refractory CLL. More than 50% has failed Rituxan combinations and more than 50% had failed fludarabine combinations. The complete response rate was 15%, the partial response rate was 53% and an additional 15% had stable disease. Two patients had complete molecular responses. The most common side effects reported were fatigue, neutropenia and thrombocytopenia. Approximately 60% had “flare reaction”—described as tender swelling of lymph nodes and rash—which was successfully treated with steroids. In-vitro studies showed an increased number of natural killer cells but no increase in apoptosis.

In 2008, Celgene reported two REVLIMID (lenalidomide) Phase II studies at the 50th American Society of Hematology Meeting. Both demonstrated high response rates and manageable side effects in patients previously untreated with symptomatic chronic lymphocytic leukemia (CLL). The studies demonstrated greater than 90 percent disease control across all evaluable patients. In 2009, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cycles, including the observation of complete responses. In 2008, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cyces, including the observation of complete responses.

It is also listed by the Drugdex compendium for CLL. The most recent noteworthy paper was in Blood 2011. Sixty patients with CLL age 65 years and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg per day as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65% including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. These are very good results for the limited reported toxicity in the ederly population.

Miller K, Czuczman MS, Dimicli L, et al. Lenalidomide (L) induces high response rates with molecular remission in patients (pts) with relapsed (rel) refractory (ref) chronic lymphocytic leukemia (CLL). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. 2006. Abstract # 6605.

Chanan-Khan AA, Miller KC, DiMicheli L, et al. Results of a phase II study of lenalidomide (L) (Revlimid) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood 2005;135a, abstract # 447.

Chanan-Khan A, Miller KC, Takeshita K, et al. Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood. 2005;106:3348-3352.

Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. Journal of Clinical Oncology. 2006;24:5343-5349.

Chen C, Paul H, Xu W, et al. A phase II study of lenalidomide in previously untreated, symptomatic chronic lymphocytic leukemia (CLL). Blood. 2008;112:23, abstract number 44.

Kornblau SM, Burger JA, Ferrajoli A.et al, Lenalidomide (REVLIMID) as initial therapy of elderly patients with chronic lymphocytic leukemia.Blood. 2011 Jul 1.

However, FDG is not a tumor-specific tracer, and numerous nonmalignant processes can result in increased FDG accumulation. Its utility in managing Rosai-Dorfman disease is not well supported by the literature. Because of the rarity of the disease, available information is restricted to case reports of use.

Treatment is not necessary in most instances, but some patients may require surgery, radiation therapy, and/or chemotherapy because of severe disease manifestations. As such, a screening PET is unlikely to provide iformation that would lead to treatment. An ideal treatment has yet to be identified.

Ruth Lim et al, FDG PET of Rosai-Dorfman Disease of the Thymus AJR 2004; 182:514

Menzel C, Hamscho N, Döbert N, Grünwald F, Kovács AF, Wolter M, Podda M.PET imaging of Rosai-Dorfman disease: correlation with histopathology and ex-vivo beta-imaging.Arch Dermatol Res. 2003 Dec;295(7):280-3.

Vectibix is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). Vectibix is specifically indicated for for the treatment of EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

Vectibix™ treatment can cause diarrhea and, in combination with irinotecan, appears to increase the incidence and severity of chemotherapy-induced diarrhea. Amgen recently discontinued a trial due to toxicity, the phase IIIb Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial is a disappointing setback. PACCE was evaluating the addition of Vectibix to a regimen of standard oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. It was halted after preliminary review of data from a pre-planned interim efficacy analysis, scheduled after the first 231 events (death or disease progression), revealed a statistically significant difference in progression-free survival (PFS) and overall survival in favor of the control arm and higher toxicity in the Vectibix arm. Total enrollment of this trial had reached 1,054. Amgen is continuing phase III trials of Vectibix as a single biologic combined with chemotherapy as a first- or second-line treatment. No other clinical trials are being modified at this time, however, Amgen is evaluating data across all trials. Vectibix is approved as a third line treatment for metastatic, refractory CRC expressing EGFR. I was not able to find any trials on Vectibix and irinotecan.

Wainberg Z, Hecht JR Panitumumab in colon cancer: a review and summary of ongoing trials. Expert opinion on biological therapy. 2006 Nov;6(11):1229-35.

Saif MW, Cohenuram M Role of panitumumab in the management of metastatic colorectal cancer. Clinical Colorectal Cancer 2006 Jul;6(2):118-24

Gibson TB, Ranganathan A, Grothey A Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clinical colorectal cancer 2006 May;6(1):29-31.

Tyagi P Recent results and ongoing trials with panitumumab (ABX-EGF), a fully human anti-epidermal growth factor receptor antibody, in metastatic colorectal cancer Clinical colorectal cancer 2005 May;5(1):21-3.

Vectibix, prescribing information

The FDA does not absolutely require EGFR positivity. This is the FDA indication: “TARCEVA monotherapy is indicated for the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy”. However, recently emerging is the approach in which all lung cancers are tested for EGFR and ALK and those positive for etiher of these mutations are treated with Tarceva or Xalkori respectively in first line. Some researchers call it “genotype directed therapy”.

Tarceva is now recommended by NCCN for first line therapy for a poor performance status with an EGFR activating mutation. In the event that EGFR was not performed, older literature, from before EGFR was available still supports the use of Tarceva in first line.

Researchers did find that certain subsets of patients were most likely to respond to erlotinib: Asians; women; patients with adenocarcinoma; and those who had never smoked. EGFR + patients have more response than EGFR negative patients but this difference was not absolute. These results confirmed those of numerous other studies. However, it is generally accepted that these factors alone do not indicate Tarceva therapy. These factors be surrogates for EGFR positivity.

In older studies that were performed without routine EGFR testing, Erlotinib (Tarceva®) prolonged survival in patients with advanced non-small cell lung cancer who had progressed after standard chemotherapy. The median survival among patients who took erlotinib was 6.7 months compared to 4.7 months for those on placebo. At one year, 31 percent of the patients taking erlotinib were still alive compared to 22 percent of those taking the placebo. There was another phase II study suggesting effectiveness front line. In an 80-patient phase 2 study, presented at the European Respiratory Society meeting, there were no complete responses among 69 evaluable patients. But 41 of the 69 patients with Stage IIIB or IV disease had a partial response (eight) or had stable disease.

In conclusion, recently routine EGFR testing became available and decisions are being made incorporating EGFR results. Older standards are appropriate when EGFR is not available.

Reck M: Treating Non-Small-Cell Lung Cancer First Line with Erlotinib Monotherapy in Elderly Patients: Discussion of a Case Series.
Onkologie 2007;30:515-518

O. Belvedere and F. Grossi
Lung Cancer Highlights from ASCO 2005
Oncologist, January 1, 2006; 11(1): 39 – 50.

Cohen, Martin H. , Johnson, John R. , Chen, Yeh-Fong , Sridhara, Rajeshwari , Pazdur, Richard
FDA Drug Approval Summary: Erlotinib (Tarceva(R)) Tablets
Oncologist 2005 10: 461-466; Noemí Reguart, Andrés Felipe Cardona, Rafael Rosell
Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer Cancer Management and Research June 2010 , Volume 2010:2 Pages 143 – 156

Revised 12/20/2010

As far as remicade, it has been reported to cause a lupus like illness. It is now in a study NCT00368264 and is clearly investigational. Tacrolimus isa new promising drug but it is currently in studies.

1.http://www.clinicaltrials.gov/ct/show/NCT00368264;jsessionid=A293025C0484E7B9F87585A9C00616A2?order=4

2. Tahir H, Rohrer J, Bhatia A, Wegener WA, Isenberg DA. Humanized anti-CD20 monoclonal antibody in the treatment of severe resistant systemic lupus erythematosus in a patient with antibodies against rituximab. Rheumatology (Oxford). 2005;44:561-562. Abstract

3. van Vollenhoven RF, Gunnarsson I, Welin-Henriksson E, et al. Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone. Scand J Rheumatol. 2004;33:423-427. Abstract

4. Tanaka Y, Yamamoto K, Takeuchi T, et al. A multi-center phase I/II trial of rituximab for treatment of refractory systemic lupus erythematosus. Program and abstracts of the American College of Rheumatology 70th Annual Meeting; November 11-15, 2006; Washington, DC. Presentation 537.

5. Jonsdottir T, Gunnarsson I, Risselada A, et al. Serological changes in patients with severe SLE treated with rituximab and cyclophosphamide. Program and abstracts of the American College of Rheumatology 70th Annual Meeting; November 11-15, 2006; Washington, DC. Presentation 539.

Nexavar is currently FDA approved for renal cell carcinoma and hepatocellular carcinoma . Sorafenib (Nexavar) is designed to interfere with growth of new blood vessels and the growth of new cancer cells.Inhibition of KIT signaling provides a direct anti-tumor effect in most GIST tumors and inhibition of VEGF receptors and PDGFR-β provide antiangiogenesis effects (similar to Sutent). Since RAF is downstream of KIT, inhibition of RAF might also contribute an anti-tumor effect. While inhibition of PDGRF-β has been reported, inhibition of PDGFRα, an alternative target in about 5% of GISTs has NOT BEEN reported.

Because sacomas generally have a poor prognosis, Nexavar can sometimes be requested for use in sarcoma.

Sarcomas can be divided into roughly two groups: chemo responsive varieties, such as Kaposi, soft tissue sarcoma, Ewings etc; poorly responsive varieties, such as chodrosarcoma and others.

Two Sorafenib (Nexavar) Clinical Trials are Currently Recruiting Sarcoma Patients in Different Locations Across the USA.

1. Phase II Study of Sorafenib in Patients With Advanced Soft Tissue Sarcomas

2. Sorafenib in Treating Patients With Soft Tissue Sarcomas

There is also an angiosarcoma trial: Sorafenib in Treating Patients With Angiosarcoma That is Locally Advanced, Metastatic, or Unable to Be Removed by Surgery, NCT00874874. There is also a Kaposi’s phase I trial and trials for GIST and other sarcoma types. Nexavar is an investigational treatment currently for sarcoma.

http://www.cancer.gov/clinicaltrials/NCI-06-C-0083

B . Kasper , T . Gil , V . D’Hondt , M . Gebhart , A . Awada Novel treatment strategies for soft tissue sarcoma Critical Reviews in Oncology/Hematology , Volume 62 , Issue 1 , Pages 9 – 15, 2007