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H. Malhotra



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    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P1.09-017 - Continuous low dose temozolamide in Brain metastasis from Lung cancer (ID 2054)

      09:30 - 09:30  |  Author(s): H. Malhotra

      • Abstract

      Background
      Metastasis of Lung cancer to Brain is associated with poor prognosis despite aggressive treatment. Available treatment options are limited beside radiotherapy as most drugs do not penetrate the blood brain barrier. Temozolamide has a good safety profile and crosses the blood brain barrier. One of the novel methods of delivering temozolamide is to use metronomic dosing which also has anti angiogenic properties, other than cytotoxic properties.

      Methods
      Eligible patients had to have confirmed Non Small Cell Lung Cancer (NSCLC) with no prior radiotherapy or radio-surgery for brain metastasis; with multiple brain metastasis. All patients were treated with Temozolamide 20mg in empty stomach twice a day continuously. Radiation was given to these patients as standard procedures. This was compared only to standard whole brain radiation. All patients continued on standard planned chemotherapy which was paclitaxel + carboplatinum and patients who had received Temozolamide were continued either till progression or unacceptable toxicity.

      Results
      41 patients - 24 men and 16 women with proven advanced Non Small Cell Lung Cancer (NSCLC) who were on treatment and developed brain metastasis, which was not operable or amicable to stereotactic radiotherapy.

      Radiotherapy (n=20) Radiotherapy & Low Dose Temozolamide (n=21)
      Median Karnofsky Score > 60 > 60
      Response Rate 7 (35%) 12 (57%)
      Complete Response 1 (5%) 5 (24%)
      Partial Response 4 (20%) 7 (33%)
      Stable Disease 3 (15%) 3 (14%)
      1 year survival rate 6 (30%) 14 (67%)
      Median Overall Survival 9.2months 17.6months
      Thrombocytopenia Grade III/IV 3 (15%) 5 (24%)
      Neutropenia Grade III/IV 1 (5%) 2 (10%)
      Anemia Grade III/IV 3 (15%) 6 (29%)

      Conclusion
      Metronomic dosing of temozolamide with concurrent whole brain radiation is an effective option in treatment of brain metastasis from Non Small Cell Lung Cancer (NSCLC). The median survival time is almost doubled. Side-effects are manageable.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-030 - Increasing Therapeutic Efficacy and Safety of Docetaxel in Lung Cancer (ID 2067)

      09:30 - 09:30  |  Author(s): H. Malhotra

      • Abstract

      Background
      Docetaxel is an accepted second line drug for NSCLC not used frequently for its side effects. VT-122 (propranolol and etodolac) which has anti-angiogenic COX-2 inhibition properties. Modifying the tumor-microenvironment and sympathetic system has anticancer activity as well as ameliorates toxicity of anticancer drugs. Docetaxel efficiency can be improved with VT-122 which possesses the above property. To increase efficacy of docetaxel and safety profile using VT-122.

      Methods
      20 (10 in each arm) patients (55-65 years) were treated with docetaxel (75mg/m[2]) with or without VT-122. VT-122 was started 7 days before giving docetaxel. Propranolol doses were titrated to maintaining heart rate around 60. Etodolac was titrated on the basis of CRP to a maximum of 1200mg.

      Results
      Overall Response seen in 4 patients (VT-122 arm) and 2 patients (docetaxel arm). 6 patients in VT-122 arm completed 6 cycles of docetaxel while in non-VT-122 4 patients completed the 6 cycles. 1 year survival was 30% vs 10%; p=0.025. Grade III/IV hematologic toxicity was decreased by 50% ie 6 cases in docetaxel arm and 3 in VT-122. In non-hematological toxicity this trend was seen for asthenia, neuropathy, skin and nail changes and weight loss.

      Conclusion
      Addition of VT-122 (propranolol and etodolac) increases efficacy of docetaxel and is cost effective.

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    P3.03 - Poster Session 3 - Technology and Novel Development (ID 152)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.03-002 - Heterogenity of Adeno carcinoma of Lung - change in Immunohistochemistry and histopathology chacter in patients treated with chemotherapy or EGFR-TKIs (ID 1356)

      09:30 - 09:30  |  Author(s): H. Malhotra

      • Abstract

      Background
      Adenocarcinoma of the lung is a heterogenous group of disease. Even within the same patient, the tumor may show, various patterns of histopathology. In fact published data suggest that only 1/3rd of lung cancer are homogenous. Although known this factor is not taken into account in treatment planning and management. It is also known that treatment induces heterogenity and change in character of the tumor.

      Methods
      46 patients of Stage IV Adenocarcinoma of Lung were studied. All patients were confirmed as Adenocarcinoma by doing IHC TTF p63. All slides were viewed by two pathologists and all patients had EGFR mutation done.IHC marker for neuro-endocrine differentiation was done i.e. Chromogranin-A and Synaptophysin. Patients were treated with chemotherapy or EGFR-TKI. Patients were re-biopsied on progression. The same set of IHC studies was done.

      Results

      IHC marker for adenocarcinoma IHC marker for squamous cell Neuro-endocrine marker
      n=46
      Pre-chemotherapy/TKI 41 (89%) 15 (32%) 17 (37%)
      Post-chemotherapy/TKI 25 (54%) 25 (54%) 29 (63%)
      n=18
      Pre TKI 16 (89%) 5 (28%) 4 (22%)
      Post TKI 8 (44%) 9 (50%) 14 (78%)
      n=28
      Pre-chemotherapy 25 (89%) 10 (36%) 13 (46%)
      Post-chemotherapy 17 (61%) 16 (57%) 15 (54%)
      Median duration of chemotherapy - 10 months Median duration of TKI - 16 months Change in character on IHC - seen in approximately 30% patients Infact change in post TKI occurring in upto 50% of patients with gain in Small Cell characters. Of the 50% patients who gained i.e. 10 patients - 7 of them also showed microscopic features of Small Cell Carcinoma of Lungs.

      Conclusion
      The study suggests that patients with advanced lung cancer have benefit from chemotherapy and TKI. On treatment and on progression there is a change in IHC and histopathology character in the patients. It occurs in close to 40% in such patients. These changes also call for changes in treatment. Hence re-biopy in such patients is essential.