Thanks for the detailed reply. After the outcome it will all make sense :-)
Noticed the Moffitt data excluded patients who didn't take iressa for >12 weeks. 1 year survival of 35% is slightly better than BR21, but that excludes the early dropouts. In a real trial, the fda certainly would want to know their outcomes :-)
>> The validity of the assessment of performance status (PS) by health professionals has not well been evaluated. We investigated for a possible discrepancy in the assessment of PS among patients, nurses and oncologists. The proportion of patients assessed as ECOG PS 0--1 by oncologist and patient was estimated to be 70 and 55%, respectively, and 200 consecutive patients with lung cancer were investigated prospectively. This accruarial [sic] goal was sufficient to have more than 85% power to detect the difference with a significance level of 5%. Further, survival analysis was conducted using the 109 patients with non-small cell lung cancer (NSCLC) of stage IIIB or IV. The percentage of patients assessed as ECOG PS 0--1 was 68% by oncologists and 53% by the patients themselves (p = 0.039, by chi-squared test). There was a significant difference among the assessment by the three groups (p < 0.001, by Friedman test). The oncologists gave the healthiest PS assessment, the nurses an intermediate assessment (although significantly healthier than patient-assessed PS), and the patients the poorest. In the Cox model, the PS assessments by the oncologists and the patients (not the nurses), as well as gender, liver metastasis, lymph node metastasis, number of organs involved with metastasis, hemoglobin, and serum lactate dehydrogenase, were significantly correlated with the survival. The cut-off of performance status associated with significant difference in survival was 0 v 1 v 2--4 in oncologist-rating, and 0--2 v 3--4 in patient-rating; this is of interest because many investigators argue that only fully ambulatory patients should be candidates for chemotherapy for advanced NSCLC. In conclusion, oncologists' assessment of PS is sufficiently valid to stratify patients in clinical trials, although the assessment is significantly different from that by patients themselves. <<
-- Definitions of ECOG Performance Status (from www.ecog.org):
GradeDescirption 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 5 Dead
This post by ‘thirdmeinvestor’ (#33738) was in reply to my post about the Tarceva monotherapy trial in the U.K. in first-line NSCLC (#msg-4680706).
[Emphasis added by Dew]
>> Here they seem to imply that the patients will be selected from pools of inoperable cases and also from chemo-intolerant situations. But oncologists have the option to use radiotherapy (RT). Don't anyone downplay the combination of RT and Tarceva. As I mentioned once before on this board, (I have to mention the mechanism, sorry Dew) EGFR1(HER1) inhibitors arrest cells in the G1 phase of cell cycle and if you receive T continuously for a while all tumor cells would be accumulated in G1. When T is withdrawn for 24-48 hours so, the effect of T disappears, and surviving cells would enter the next phase, DNA synthesis phase all at once. This is the time they should deliver RT because cells in S phase is most sensitive to radiation because RT cuts replicating DNA double helix at many many places and cells cannot repair very well in S phase. You should not take T for a day or two after RT is delivered because again T would arrest cells to allow the time to repair DNA damage. All oncologists know this, but they don't apply the knowledge in trials, most likely because of the constraint imposed on the control patients who should get the best standard care. You may recall ASCO-reported fantastic synergy between Erbitux and RT in treating head & neck tumors. One can devise many interesting treatment options by varying the RT dose and the time interval between successive RT doses, T or E has to be inserted in between. The cell cycles in human tumors are days long, so a weekly schedule of repeating the combo until all tumor cells are killed. Sadly, all trials I read so far administer T everyday. One of the reasons that Chemo + T or Chemo + Iressa did not work is because the patients had taken the pill continuously. <<
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