U.S. patent application number 13/978923 was filed with the patent office on 2013-11-07 for pharmaceutical composition for treating cancer.
The applicant listed for this patent is Bakulesh Mafatlal Khamar, Indravadan Ambalal Modi. Invention is credited to Bakulesh Mafatlal Khamar, Indravadan Ambalal Modi.
Application Number | 20130295648 13/978923 |
Document ID | / |
Family ID | 54264167 |
Filed Date | 2013-11-07 |
United States Patent
Application |
20130295648 |
Kind Code |
A1 |
Khamar; Bakulesh Mafatlal ;
et al. |
November 7, 2013 |
PHARMACEUTICAL COMPOSITION FOR TREATING CANCER
Abstract
The present invention relates to increase in survival of mammals
suffering from desmocollin 3 expressing cancers. Mycobacterium w is
administered to mammals suffering from desmocollin-3 expressing
cancers. The administration of Mycobacterium w results in control
of tumor and improvement in survival. Mycobacterium w can also be
used along with other therapeutic agent(s)/modalities as per the
requirement. The squamous type of non small cell lung cancer is
known to be desmocollin-3 expressing cancer. Other cancers also
express desmocollin-3.
Inventors: |
Khamar; Bakulesh Mafatlal;
(Ahmedabad, IN) ; Modi; Indravadan Ambalal;
(Ahmedabad, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Khamar; Bakulesh Mafatlal
Modi; Indravadan Ambalal |
Ahmedabad
Ahmedabad |
|
IN
IN |
|
|
Family ID: |
54264167 |
Appl. No.: |
13/978923 |
Filed: |
January 10, 2012 |
PCT Filed: |
January 10, 2012 |
PCT NO: |
PCT/IB2012/050120 |
371 Date: |
July 10, 2013 |
Current U.S.
Class: |
435/253.1 |
Current CPC
Class: |
A61K 2039/585 20130101;
A61P 35/00 20180101; A61K 39/04 20130101; A61K 2039/521 20130101;
A61K 45/06 20130101; A61P 37/04 20180101; A61K 35/74 20130101; C12N
1/20 20130101 |
Class at
Publication: |
435/253.1 |
International
Class: |
A61K 35/74 20060101
A61K035/74; C12N 1/20 20060101 C12N001/20 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 11, 2011 |
IN |
92/MUM/2011 |
Claims
1. Mycobacterium w for use in the treatment of a desmocollin-3
expressing cancer.
2. Mycobacterium w for use according to claim 1, wherein said
cancer is a squamous type of non small cell lung cancer.
3. Mycobacterium w for use according to claim 1, wherein cancer
cells of the subject suffering from said cancer have been
determined to express desmocollin-3.
4. Mycobacterium w for use according to claim 1, wherein said
Mycobacterium w increases the survival of the subject suffering
from a desmocollin-3 expressing cancer.
5. Mycobacterium w for use according to claim 1, wherein said
Mycobacterium w is used in a dosage of more than 10.sup.6 cells per
dose.
6. Mycobacterium w for use according claim 1, wherein said
Mycobacterium w is used in combination with at least one other
therapeutic agent or modalities.
7. Mycobacterium w as claimed in claim 6, wherein said at least one
other therapeutic agent or modalities is a chemotherapeutic agent.
Description
FIELD OF INVENTION
[0001] The present invention relates to improving outcome of
current therapies for Non Small cell Lung Cancer, particularly that
of Squamous cell carcinoma of the lung. The present invention
further relates to providing a novel therapy for tumors expressing
desmocollin-3.
BACKGROUND OF INVENTION
[0002] Lung cancer is the leading cause of cancer-related Deaths
world wide with 1.2 million new cases diagnosed every year and with
1 million deaths being recorded worldwide in 2001. Lung cancer is
divided into two main groups, small cell lung cancer and non-small
cell lung cancer. Approximately 75%-85% of these patients have non
small cell lung cancer and rest have small cell lung cancer. Non
small cell lung cancer (NSCLC) has been further classified as per
histology into a number of different types, including inter alia
adenocarcinoma, squamous cell carcinoma and large cell carcinoma
adenocarcinoma are often found in an outer area of the lung.
Squamous cell carcinomas are usually found in the center of the
lung next to an air tube (bronchus). Large cell carcinomas can
occur in any part of the lung. They tend to grow and spread faster
than the other two types.
[0003] Immunohistochemistry (IHC) refers to the process of
detecting molecules in cells of a tissue section by exploiting the
principle of antibodies binding specifically to molecules in
biological tissues. Immunohistochemical staining is widely used in
the diagnosis of abnormal cells such as those found in cancerous
tumors.
[0004] IHC is also widely used in basic research to understand the
distribution and localization of biomarkers and differentially
expressed proteins in different parts of a biological tissue.
[0005] Desmocollin-3 is expressed in squamous variety of NSCLC and
its presence, as detected for example by IHC, is typically used to
differentiate squamous cell carcinoma from Adenocarcinoma. Thyroid
transcription factor 1 (TTF-1) is expressed in Adenocarcinoma of
the Lung and its presence, as detected for example by IHC, is
typically used to differentiate Adenocarcinoma from Squamous cell
carcinoma. The basis of Immunohistochemistry is to detect presence
of expression of a particular biomarker. Desmocollin-3 and TTF-1
are such biomarkers which are specific for Squamous cell carcinoma
and Adenocarcinoma of the Lung respectively. TTF-1 is a protein
that regulates the transcription of genes. Desmocollin-3 belongs to
the Cadherin group of cell adhesion molecules. Desmocollins are
calcium dependent adhesion molecules. Desmocollin 1, 2 and 3, are
desmosomal component typically found in pseudostratified and
stratified epithelia. Desmocollin-3 is expressed on basal most
layers of stratified epithelia and its expression decreases
gradually in the suprabasal layers. The expression of RNA specific
to desmocollin gene is associated with the expression of
desmocollins. It has been observed that cells containing a specific
desmocollin subtype tend to cluster together to the exclusion of
other types.
[0006] Historically, first-line treatment for patients with
advanced NSCLC has been platinum-based doublet chemotherapy in
combination with a third-generation cytotoxic compound such as
gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, Ind.),
Paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, N.J.) or
Docetaxel (Taxotere; Sanofi-Aventis, Bridgewater, N.J.). Clinical
trials of a platinum based therapy in combination with any of these
agents demonstrated comparable efficacy, and meta-analyses showed
that these regimens offered superior survival and symptom
palliation versus best supportive care. The study conducted by
Eastern Cooperative Oncology Group (ECOG) comparing four
platin-based, two-drug chemotherapy regimens in more than 1100
patients suggests no significant differences in overall survival
among the groups.
[0007] The first line therapy is offered irrespective of histology
of the tumor. The efforts are made to improve the out come of first
line therapy without any success.
[0008] Recently Bevacizumab is approved as add on therapy to first
line therapy for non squamous cell lung cancer. Bevacizumab has
been demonstrated in combination with first line therapy to improve
outcomes over those seen with first line therapy alone in the
treatment of advanced non squamous NSCLC. The two large, phase III,
randomized trials leading to these relevant results have
administered bevacizumab with carboplatin plus paclitaxel and
cisplatin plus gemcitabine as first line therapy
[0009] Similarly it is also observed that pemetrexed is useful in
non squamous carcinoma of lung. Non squamous patients treated with
pemetrexed-based therapy experienced longer survival than the
comparators (HR, 0.78 and 0.84 respectively), whereas squamous
patients had shorter survival (HR, 1.56 and 1.23 respectively). It
is recommended that it should not be used in squamous cell
carcinoma of lung as it worsens the prognosis.
[0010] Thus, histology of tumor plays significant role in
improvement with first line therapy by addition of a new drug. IHC
helps in defining characteristics of cell types and also deciding
histology subtype of a tumor as it helps in choosing appropriate
therapy.
[0011] There is a significant improvement in outcome of non
squamous lung cancer recently but no further improvement is seen in
patients suffering from squamous cell carcinoma.
[0012] Immune surveillance of body is responsible for eliminating
cancer cells before they manifest as tumor. Tumor growth is
associated with escape from immune surveillance due to immune
suppression by tumor or other causes. Immuno-suppression is known
to be proportional to size of a tumor. Immunotherapy helps in
reconstituting immunity.
[0013] Immunotherapy may result in a robust reconstitution of
immunity which is able to overcome existing immuno-suppression
under such circumstances tumor is eliminated. Initially this will
manifest as regression of a tumor. This is typically observed when
tumor burden is small. In case immune response generated is not
adequate to overcome immuno-suppression but achieves equilibrium
with immuno-suppression, tumor doesn't grow in size but remains
stationary. There is improvement in survival in absence of tumor
response.
[0014] Immunotherapy may be used alone or in combination of other
cancer therapies for cancer.
DETAIL DESCRIPTION OF FIGURE
[0015] FIG. 1 shows survival in all patient(s) with non small cell
lung cancer.
[0016] FIG. 2 shows survival in all patient(s) with
adenocarcinoma.
[0017] FIG. 3 shows survival in all patient(s) with squamous cell
carcinoma of lung.
[0018] In all the figures the test arm is having better survival
compared to central arm. The test arm is having higher value as
survival at end of study period compared to control arm.
OBJECT OF THE INVENTION
[0019] An object of present invention is to provide a therapy for
desmocollin-3 expressing cancers.
[0020] Another object of present invention is to provide a therapy
for squamous type of non small cell lung cancer, which is a
desmocollin-3 expressing cancer.
[0021] Another object of present invention is to provide a therapy
for non small cell lung cancer, particularly the squamous type.
[0022] Yet another object of present invention is to improve
survival of patients suffering from desmocollin-3 expressing
cancers.
[0023] Yet another object of present invention is to provide a
therapy for patients suffering from desmocollin 3 expressing
cancers using Mycobacterium w.
[0024] Yet another object of present invention is to provide a
therapy for patients suffering from desmocollin-3 expressing
cancers using Mycobacterium w along with other cancer
therapies.
[0025] Yet another object of present invention is to improve
survival of patients suffering from desmocollin-3 expressing
cancers using Mycobacterium w along with conventional therapy.
DETAILED DESCRIPTION OF THE INVENTION
[0026] Surprisingly it is observed that immune cells generated
following administration of Mycobacterium w (Mw) to a mammal
express desmocollin-3 (see Example 2). Thus, it appears that Mw
causes the appearance of desmocollin-3 expressing immune cells,
which may be by causing the generation of new immune cells, or by
causing existing immune cells to express desmocollin-3. The immune
cells are Peripheral blood mononuclear cells (PBMCs). Desmocollin-3
is responsible for anchoring of activated immune cells on
cells/tissues/tumors.
[0027] Surprisingly it is observed that therapy using
pharmaceutical compositions containing Mycobacterium w when
administered to patients suffering from desmocollin-3 expressing
cancers results in significant advantage in tumor control and
survival. Therapy using pharmaceutical compositions containing
Mycobacterium w administered to patients suffering from non small
cell carcinoma was particularly effective; a clinically and
statistically significant benefit is seen in patients suffering
from squamous cell carcinoma which are known to express desmocollin
3.
[0028] The present invention provides Mycobacterium w for use in
treating desmocollin-3 expressing cancers, preferably squamous cell
carcinoma, which is a histological variety of non small cell lung
cancer. In particular, the invention is concerned with improving
the survival of patients having desmocollin-3 expressing
carcinoma.
[0029] In another embodiment, the invention provides Mycobacterium
w for use in treating NSCLC, preferably squamous cell
carcinoma.
[0030] The inventors through extensive experimentation have found
that administration of Mycobacterium w improves median survival as
well as overall survival of such patients. The median overall
survival is preferably improved by at least 10, 20, 30, 40, 50, 60,
70, 80, 90, 100 or 110 days, e.g. by about 70-110 or 90-110 days.
The median overall survival is preferably improved by a factor of
at least 1.1, 1.2, 1.3, 1.4 or 1.5, most preferably about 1.5.
[0031] The median overall survival is preferably at least 240, 250,
260, 270, 280, 290, 300, 310, 320, 330, 30, 350 or 360 days, e.g.
290-365 or 300-360 days from the start of the treatment.
[0032] The patient may have any kind of tumor expressing
desmocollin-3. The tumor can be of any stage. The tumor may be
surgically amenable or surgically non amenable.
[0033] The patient may have any stage of Non-Small Cell Lung
Cancer, preferably of the squamous carcinoma type, but preferably
the patient has an advanced stage of the cancer, such as stage IIIB
or IV. Preferably, the patient has an ECOG (Eastern Cooperative
Oncology Group) performance status of 0 or 1. The patient is
preferably human.
[0034] The inventors have found that cells of human embryonic lung
carcinoma, human skin malignant melanoma, hepatic carcinoma and
several cell types of human pancreatic adenocarcinoma are
desmocollin-3 positive. The therapy of the invention is preferably
directed to one or more of these cancer types. The inventors have
also found that some patients with bladder cancer have bladder
cancer cells that are desmocollin-3 positive. Thus, patients that
have bladder cancer cells that are desmocollin-3 positive may
benefit from treatment with Mw according to the present
invention.
[0035] The invention therefore provides a novel approach to
treating cancer. Cancers or samples thereof may be screened in vivo
or in vitro to assess desmocollin-3 expression, for example by
immunohistochemistry, RNA analysis and the like. The results of the
analysis may be used to determine what treatment the subject should
receive. In particular, based on the detection of desmocollin-3
expression, a determination may be made that the subject should be
treated with Mw. Thus, there is provided a method of determining
what treatment a cancer patient should receive, said method
comprising (a) testing whether the cancer of said patient expresses
desmocollin-3; and (b) if said cancer expresses desmocollin-3,
determining that said patient should be treated with Mw.
Alternatively viewed, there is provided a method of diagnosing that
a cancer patient is in need to treatment with Mw, said method
comprising (a) testing whether the cancer of said patient expresses
desmocollin-3; and (b) if said cancer expresses desmocollin-3,
determining that said patient should be treated with Mw. Any of
said methods may also comprise (c) treating said patient with
Mw.
[0036] Thus, Mw is preferably used to treat a patient whose cancer
has been determined to express desmocollin-3. Thus, cells of the
cancer of said patient have preferably been analysed to determine
that they express desmocollin 3.
[0037] In the therapy according to the invention, Mycobacterium w
may be used alone or in combination with one or more active agents
such as chemotherapeutic agents. The therapeutic agent used in
combination with Mycobacterium w is selected by a skilled person in
the art as per the requirement based on type of cancer, stage of
cancer etc. Preferably, the chemotherapeutic agent is selected from
Paclitaxel and/or Cisplatin,
[0038] In accordance with present invention, also provided is a
pharmaceutical composition comprising Mycobacterium w and a
pharmaceutically acceptable excipient or diluent. The
pharmaceutical composition may also comprise a chemotherapeutic
agent, which is preferably selected from Paclitaxel and/or
Cisplatin.
[0039] Mycobacterium w is preferably used in killed form, e.g. heat
killed. The pharmaceutical composition is preferably formulated to
provide a dose of more than 10.sup.6 cells of Mycobacterium w per
dose. The Mycobacterium w is preferably administered in a dosage of
at least 0.5.times.10.sup.6, at least 0.5.times.10.sup.7, or
0.5.times.10.sup.8, orranging from 0.5.times.10.sup.6 to
0.5.times.10.sup.11, more preferably 0.5.times.10.sup.8 to
0.5.times.10.sup.10 most preferably about 0.5.times.10.sup.9.
Mycobacterium w may be administered by any convenient route known,
e.g. intravenously (IV) or intradermally.(ID) The dosage schedule
may for example involve administration twice or once a week, once
every two weeks, once a month, or twice in a 21 day cycle. If used
in combination with other agents the time of administration of
Mycobacterium w in relation to other therapeutic agents/modalities
is decided by person skilled in the art, Mycobacterium w is
preferably administered at least 1 week prior to the first cycle
and every 2nd and 3rd week of each cycle when paclitaxel and/or
cisplatin is used.
[0040] The cycle for other therapeutic agents/modalities, its
duration, frequency, interval between two administrations of
therapeutic agent/modalities is decided by the person skilled in
the art based on requirement. The cycle is preferably of about 21
days for most of the chemotherapeutic agents including paclitaxel
and/or cisplatin. The total numbers of cycles for chemotherapy are
4 or more. The numbers of cycles are decided person skilled in the
art based on response to therapy, side effects and tolerance to
therapy etc. For chemotherapy using paclitxel and/or cisplatin as
first line therapy in non small call lung cancer preferably a total
of about 4 cycles is used.
[0041] Following examples demonstrate the present invention without
limiting the scope of the invention:
EXAMPLE 1
Pharmaceutical Composition as per Present Invention
TABLE-US-00001 [0042] Each dose of 0.1 ml contains: Mycobacterium w
(heat killed) 0.50 .times. 10.sup.9 Sodium Chloride I.P. 0.90% w/v
Thiomerosal I.P. 0.01% w/v (As a Preservative) Water for Injection
I.P. q.s to 0.1 ml
EXAMPLE 2
[0043] The healthy human were randomized to receive Mycobacterium w
0.1 ml and PBS (Control) intradermally. After 7 day blood was
withdrawn and PBMCs were isolated. The total RNA was extracted from
the isolated. The total RNA was used to generate microarray data
against Global Human microarray. The data was interpreted as fold
change over control. The data shows that desmocollins-3 gene is
over expressed by four fold. There is no effect on other
desmocollins. There is also no effect on TTF-1 gene.
EXAMPLE 3
Cancer Cells Expressing Desmocollin-3
[0044] The following is a list of cell lines which were evaluated
for desmocollin-3 (Table 1)
TABLE-US-00002 TABLE 1 Sr. Immuno- No. Cells Type fluorescence
PANCREATIC CANCER 1 Panc-1 Human Pancreatic Adenocarcinoma Positive
2 AsPc-1 Human Pancreatic Adenocarcinoma Positive 3 Sw 1990 Human
Pancreatic Adenocarcinoma Positive 4 Mia-PaCa2 Human Pancreatic
Adenocarcinoma Negative LUNG CANCER 5 L-132 Human Embryonic lung
carcinoma Positive 6 A549 Human alveolar Adenocarcinoma Negative
SKIN CANCER 7 A375 Human skin malignant melanoma Positive COLON
CANCER 8 HT-29 Human colorectal adenocarcinoma Negative LIVER
CANCER 9 Hep 3B Hepatic Carcinoma Positive
EXAMPLE 4
Desmocollin-3 Expressions by Immunohistochemistry
[0045] Sections of tumors removed during surgery were stained for
presence of or absence of desmocollin-3. The thin paraffin sections
of tumors were stained using standard protocol for Immuno
histochemistry using antibodies specific for DSC 3. The brief
staining procedure includes washing with PBS. Followed by staining
with 1:1000 diluted primary antibody (Anti DSC-3 goat polyclonal)
for overnight and staining with secondary antibody (Goat anti-mouse
IgG-FITC) for 30 minutes.
[0046] The findings are in a table. It is seen that none of breast
cancers, Head & Neck Cancer, Colon cancer samples expressed
desmocollin-3 while one of the three from a recurrent bladder
cancer.
TABLE-US-00003 TABLE 2 Sr No of samples No of samples No Type of
cancer No of samples positive negative 1 Head and neck 7 0 7 2
Bladder 3 1 2 3 Colon 8 0 8 4 Breast 7 0 7
EXAMPLE 5
Efficacy of Pharmaceutical Composition in Squamous Cell Lung
Cancer
[0047] In an open label, multicentric, randomized, comparative
controlled clinical trial, Mycobacterium w was evaluated in
combination with Paclitaxel and Cisplatin for its effect on
improvement in overall survival in patients with advanced non small
cell lung cancer.
TABLE-US-00004 TABLE 3 Agent Dose Route Schedule Paclitaxel 175
mg/m.sup.2 IV over 3 hrs before Day 1 of each Cisplatin cycle
Cisplatin 100 mg/m.sup.2 IV over a hr after Day 1 of each
completion of cycle Paclitaxel through separate IV line
Mycobacterium w 0.1 ml* Intradermal 0.1 ml At least 1 week over
each deltoid prior to first on first visit & cycle & every
0.1 ml subsequently 2.sup.nd & 3.sup.rd wek of all the cycles
*Containing 0.50 .times. 10.sup.9 heat killed Mycobacterium w.
[0048] The study was conducted on total 221 patients.
[0049] Dosage Schedule:
[0050] Test arm received Paclitaxel Cisplatin by intravenous
infusion on day 1 of a 21 days cycle for a total of 4 cycles. In
addition, Mycobacterium w was given intradermally at least one week
prior to the first cycle of chemotherapy and then in every second
and third week of all the cycles of chemotherapy.
[0051] Control arm received only chemotherapy
(Paclitaxel+Cisplatin) by intravenous infusion on a 21 days
cycle.times.4 cycles.
[0052] The Patients Enrolled in the Trial Met Following Inclusion
Criteria:
[0053] Histologically or cytologically confirmed Non-Small Cell
Lung Cancer, Stage IIIB or IV.
[0054] Age: 18 years and above
[0055] ECOG status in 0-1 range
[0056] Absolute neutrophil count.gtoreq.1500/mm.sup.3, Platelet
count.gtoreq.1,00,000/mm.sup.3
[0057] Hemoglobin.gtoreq.9.0 g/dL
[0058] AST and ALT.ltoreq.2.5 times Upper Limit of Normal (ULN) (5
times ULN if liver metastasis present)
[0059] Bilirubin not greater than 1.5 times ULN (3 times ULN if
liver involvement).
[0060] Creatinine.ltoreq.upper limit of normal (ULN)
[0061] Negative pregnancy lest for women of child bearing potential
prior to entry into the trial
[0062] Ability to understand and the willingness to sign a written
informed consent document
[0063] Following patients were excluded:
[0064] Patient who had received cytotoxic chemotherapy or
radiotherapy prior to entering the study
[0065] Patient with systematic brain metastasis
[0066] History of allergic reaction attributed to Paclitaxel,
Cisplatin or Mycobacterium w or any of theft ingredients
[0067] Pregnant women or nursing women
[0068] Uncontrolled intercurrent illness that would limit
compliance with study requirements
[0069] HIV positive patients
[0070] Previous splenectomy
[0071] Efficacy Analysis:
[0072] a. All the analysis reported is as per protocol. Survival
was defined as the time from randomization to death from any cause,
and progression free survival as the time from randomization to
documented disease progression or death.
[0073] Results:
[0074] b. A total of 221 patients were enrolled in the trial, of
which 109 were allocated to the test arm and 112 to the control
arm. Both the groups were comparable in all baseline
characteristics (Table-4).
TABLE-US-00005 TABLE 4 Baseline Characteristics Test Control
Parameters N = 109 N = 112 Sex [No. (%)] Female 18 (16.6%) 14
(12.5%) Male 91 (83.4%) 98 (87.5%) Age (yrs) 56.4 .+-. 11.0 56.9
.+-. 10.4 Weight (kg) 49.8 .+-. 10.7 50.5 .+-. 8.9 ECOG I 63
(57.8%) 66 (58.9%) ECOG 0 46 (42.2%) 46 (41.1%) Stage of Disease
IIIB 54 (49.54%) 61 (54.46%) Stage of Disease IV 55 (50.46%) 51
(45.54%) NSCLC Type Adenocarcinoma 45 50 Squamous Cell Carcinoma 19
24 Others 42 34 Large Cell Carcinoma 3 4
[0075] Use of Mycobacterium w is associated with significant
improvement in overall survival (FIG. 1) in test arm in comparison
to the control arm. Median over all survival was 233 days in
control arm and was improved by 66 days to 299 days in test arm in
subjects who completed all four cycles of chemotherapy as planned
(HR=0.64; 95% Cl: 0.41-0.98; p=0.0438). As per intent to treat
analysis it was 196 days in control arm and improved by 12 days to
208 days in test arm(HR=0.86; 95% Cl: 0.63-1.19; p=0.380). This was
clinically not relevant and statistically not significant.
[0076] Improvement in survival is more in patients with Squamous
cell carcinoma (FIG. 2) in comparison to those with Adenocarcinoma
(FIG. 3), with median survival 364 days and 288 days, respectively
in those who completed four cycles of chemotherapy. The difference
in median survival in relation to control group was 110, and 61
days, respectively. The difference in survival for those patients
who completed four cycles of chemotherapy was statistically
significant for squamous cell carcinoma (HR=0.40; 95% Cl:
0.17-0.96; p=0.0414) but was not statistically significant for
adenocarcinoma (HR=0.68; 95% Cl: 0.36-1.29; p=0.2467).
[0077] Similar findings are seen in intent to treat (ITT) analysis.
Improvement in survival appears to be more in patients with
Squamous cell carcinoma in comparison to those with Adenocarcinoma,
with median survival 229 days and 213 days, respectively. The
difference in median survival in relation to control group was 57,
and 14 days respectively. The difference in survival for patients
with squamous cell carcinoma was statistically significant
(HR=0.54; 95% Cl: 0.31-0.94; p=0.0312) but was not statistically
significant for adenocarcinoma (HR =0.95; 95% Cl: 0.57-1.57;
p=0.8567).
[0078] Thus clinically relevant and statistically significant
improvement in survival is seen with squamous cell carcinoma and
not in adenocarcinoma by intent to treat analysis as well as
analysis for patients who completed four cycles of chemotherapy as
planned.
EXAMPLE 6
Efficasy of Mw in Desmocollin-3 Expression Tumor
[0079] In 11 patients with BOG refractory bladder cancer was
performed TUR (Transurethral resection). Following 0.1 ml Mw was
administered intradermally every two weeks for six administrations
and every 4 weeks for six administrations and every 8 week for
three administrations. Patients achieved remissions lasting for
more than 15 months were having tumors which were desmocollin-3
positive. Others having recurrence of a tumor in less than three
months had desmocollin-3 negative tumors.
* * * * *