CHEMICAL AND ENGINEERING
NEWS Cancer: Challenge from Antibiotics
i 1 I
News about Mitomycin Q Parke, Davis unveils Actinobolin at antibiotics symposium
JYLEDICAL
SCIENCE
took
a
deeper
plunge into a new era of the antibiotics a g e . T h e occasion: tlie sixth annual antibiotics symposium held in Washington, D. C , which this year coincided* with the 30th anniversary of the discovery of penicillin, and the 10th anniversary of broad-spectrum antibiotics. Cancer-fighting antibiotics held the spotlight this year, as performance of three candidates was detailed: Parke, Davis introduced Actinobolin, Upjohn trotted out details on Streptovitacin A, and a team of Japanese scientists created a stir with reports of success using Mitomycin C in humans. Other successes in man's war against disease were heralded at t h e three-clay symposium. From Pfizer came news of successful treatment of schistosomiasis (a worm infestation spread by fresh water snails) with glucosamine, a form of sugar. T h e disease ranks as the world's second greatest killer, just after malaria. Sulfa drugs, too, h a d their day. A new, long-acting compound, sulfadimethoxine, was introduced. Studies
thé? n e w s m a g a z i n e ôf t h e c h e m i c a l w o r l d VOLUME 36, DUMBER 4 3
J
OCTOBER 27» 1 9 5 6
Antibiotics Raise Their Score Against Cancer (in
Tumor rats,
mici\
hamsters)
Actinobolin Mitomycin C lOOO mgJkgJdmj 2 mgJkg.Ulay
1 1
I
Sarcoma 1 8 0
db
I
S a r c o m a 1 8 0 (ascitic)
+ ++
+ +++
I
Sarcoma Τ 2 4 1
—
dr
I
1
Sarcoma M A 3 8 7
db
I
1
Ehrlich c a r c i n o m a
db
=b
1
1
Ehrlich c a r c i n o m a (ascitic)
+++
+++
j
1
Bashford carcinoma 6 3
+
I
1
Adenocarcinoma E0771
+
1
Miyono adenocarcinoma
db
1
Carcinoma 1 0 2 5
-f+·
++ ++ +++
I ! I
1
Lewis b l a d d e r c a r c i n o m a
—
db
Ι
1
Lewis lung c a r c i n o m a
+
1
1
W a g n e r osteogenic sarcoma
1
R i d g w a y osteogenic sarcoma
—
++ ++ +
j Ι
j
Mecca lymphosarcoma
—
±
ι
1
G a r d n e r lymphosarcoma
—
+
ι
1
Harding-Passey
—
1
Glioma 26
++
1
Friend virus l e u k e m i a
=fc
1
Flexner-Jobling carcinoma
++ ++ ++ + +++
I I J I
J
W a l k e r carcinosarcoma 2 5 6
++
+ + 4-
1
1
Jensen s a r c o m a
db
J
Murphy-Sturm lymphosarcoma
zfc
1
C r a b b hamster sarcoma
+++ ++ ++
1 1 1
1 J I 1 ι
Key: — -± + -|—|-+- + -f-
1
Source:
melanoma
Indicates Indicates Indicates Indicates indicates
I 1
no effect slight i n h i b i t i o n moderate i n h i b i t i o n marked inhibition complete i n h i b i t i o n
K. Sugiura, Sloan-Kettering Institute for Cancer Research
OCT.
2 7,
1958
C&EN
j
19
Parke, Davis researchers (left to right) Theodore ÏÏL Haskell, Salvatore A . Fusari, and Robert F . Pittillo describe Actinobolin, a new anti-tumor antibiotic
with Madribon, Hoffmann-LaRoche's name for t h e drug, at pediatric hospitals are encouraging, researchers r e port. Some pluses—low toxicity and a dosage of only one tablet a d a y . But the nearly 1000 antibiotics e x perts heard sobering news, too. Nearly four sessions, including two panel d i s cussions, were devoted to t h e staphylococci disease problem (many strains of staphylococcus aureus show resistance to antibiotics). Consensus here—the problem is becoming more serious e v e r y day, and no clear-cut answer is at h a n d yet. • Cancer. From a team of Japanese scientists comes w o r d that Mitomycin C, an antibiotic isolated from Streptomyces caespitosus, has racked u p a high score against a wide variety of tumors in h u m a n patients. T h e trials covered 82 patients; in 10, Mitomycin C was given to prevent recurrence of malignancy after radical surgery, b u t in 72 other patients treated with t h e drug, the malignancies w e r e so advanced t h a t radical surgery was impossible, reports Yeamon Shiraha of 20
C & ΕΝ
OCT.
2 7.
19 5 8
t h e O s a k a ( J a p a n ) City University M e d i c a l School. Results—one patient is completely recovered, nine showed excellent progress, says Shiraha. Of t h e S 2 cancer patients treated with Mitomycin C, 25 showed some improvement, as evidenced b y regression of tumors. Side effects, while serious, apparently aren't an insurmountable hurdle. Shiraha says leucopenia—lowering of t h e white blood cell count—is t h e one seen most frequently. Nearly 8 4 % of the patients w h o got Mitomycin C intravenously s h o w e d evidence of leukopenia, while the score w a s 679k for those getting the d r u g intraarterialiy. But all of t h e latter group recovered within three weeks after medication was stopped, with SOr/o of t h e other group recovering in t h e same interval. Shiraha tags Mitomycin C as relatively low in toxicity, r e c o m m e n d s t h a t i t be tried against more tumors—leukemias and ehorîopithelioma, for example. Since Mitomycin C h a s , u p until now, been available only in Japan, widespread trials have been h a r d to
set up. But hard on tlie he&eels of Shiraha's report at the syinqposium, Bristol L a b s a n n o u n c e d t h a t il \3%.*as producing t h e antibiotic, thuts nistking it available in the U. S. for tfheiierst time. Bristol is making limited quantities u n d e r a contract with tlic Cancer C h e m o t h e r a p y National Service? Center a t the National Institutes of Health. C C N S C will allocate test aincziunts to* investigators. Results from clinical tests at t h r e e U . S. ittstitutâoiis «avili heir* determine w h a t place Mitomycin C lias in anti-cancer therapy. • N e w Antibiotic Unveiled— Mores cancer n e w s was to come Iran * h e symposium. Parke, Davis stripped! the veil of secrecy from its latest entr-y in the? antibiotics US. cancer war, Named Actinobolin, this chemicad, loto, is derived from a species of Str*^piom®ujces> So far, Actinobolin h ^ s be?en used only against tumors in amimafe. Mos=t results h e r e a r e encouraging, It shows activity against a w i d e ramge m$ tumors; b u t relatively high doses—aroimnd 10OC) rng./kg. day—seem to be* necessary fo>r maximum results. Furtther, best results are seen against young tumors— 2 4 hour implants—with iresulfcs against well established tumors not itioo good. Researchers at Sloan-KZettenng Instit u t e for Cancer ResearcSh saw that mo cross-resistance to other «aiti-tumor agents, such as o-ihiforouiaracil amd amethopterin, seems to dlevclcnip in tes=ts against mouse leukemiats, thwe conclusion b e i n g t h a t Aciinul**uïiu «acts by a different mechanism. Parkse, Davis* Robert F . Pittillo says fusrtlier-,. extensive clinical trials are in the w o r k s . • Upiohn, Too. The jprolifumc Strcpûomyces has yielded a potential anticancer agent for Upjohm, to»o. Wli^n beer solids from a Stnepïowwwjces fermentation s h o w e d ability t o inhibit Sarcoma 180, Upjohn scie«itists d*.ig deeper. From six corrmponesants in t h e beer t h a t showed som^ activity, U p john came u p w i t h Stxeptovitacin A. In animals, this compound inhibits a wide range of tumors, esspccuLally youuig ones, with best activity a g a i n s t Sarcoma ISO. But Upjohn's John B . Fiesld told t h e symposium the line bertweesi a n effective dose a n d a toxic dose of Streptovitacin A is narrow; further, the cheamical is only a growtra. intaibitor, ïiot carcinolytic. Upjohn plans t o conrtimie^ studies on Streptovitacin A. Early enophasis w i l l go on studies of dosa-ge s c h e d u l e s to allow prolonged treatment: of established tumors.
